---
_id: '15016'
abstract:
- lang: eng
text: 'The development, evolution, and function of the vertebrate central nervous
system (CNS) can be best studied using diverse model organisms. Amphibians, with
their unique phylogenetic position at the transition between aquatic and terrestrial
lifestyles, are valuable for understanding the origin and evolution of the tetrapod
brain and spinal cord. Their metamorphic developmental transitions and unique
regenerative abilities also facilitate the discovery of mechanisms for neural
circuit remodeling and replacement. The genetic toolkit for amphibians, however,
remains limited, with only a few species having sequenced genomes and a small
number of transgenic lines available. In mammals, recombinant adeno-associated
viral vectors (AAVs) have become a powerful alternative to genome modification
for visualizing and perturbing the nervous system. AAVs are DNA viruses that enable
neuronal transduction in both developing and adult animals with low toxicity and
spatial, temporal, and cell-type specificity. However, AAVs have never been shown
to transduce amphibian cells efficiently. To bridge this gap, we established a
simple, scalable, and robust strategy to screen AAV serotypes in three distantly-related
amphibian species: the frogs Xenopus laevis and Pelophylax bedriagae, and the
salamander Pleurodeles waltl, in both developing larval tadpoles and post-metamorphic
animals. For each species, we successfully identified at least two AAV serotypes
capable of infecting the CNS; however, no pan-amphibian serotype was identified,
indicating rapid evolution of AAV tropism. In addition, we developed an AAV-based
strategy that targets isochronic cohorts of developing neurons – a critical tool
for parsing neural circuit assembly. Finally, to enable visualization and manipulation
of neural circuits, we identified AAV variants for retrograde tracing of neuronal
projections in adult animals. Our findings expand the toolkit for amphibians to
include AAVs, establish a generalizable workflow for AAV screening in non-canonical
research organisms, generate testable hypotheses for the evolution of AAV tropism,
and lay the foundation for modern cross-species comparisons of vertebrate CNS
development, function, and evolution. '
acknowledgement: "We would like to extend our thanks to members of the Sweeney, Tosches,
Shein-Idelson,\r\nYamaguchi, Kelley, and Cline Labs for their contributions to this
project, discussion and support.\r\nWe additionally thank the Beckman Institute
Clover Center and Viviana Gradinaru (Caltech),\r\nKimberly Ritola (UNC NeuroTools),
Flavia Gama Gomez Leite (ISTA Viral Core), and Hüseyin\r\nCihan Önal (Shigemoto
Group, ISTA) for their consultation and assistance regarding AAVs, as\r\nwell as
Andras Simon and Alberto Joven for feedback and discussions on AAVs in Pleurodeles.\r\nTo
do these experiments, we have also benefited from the tremendous support of our
animal care and imaging facilities at our respective institutions, as well as the
amphibian stock centers\r\n(National Xenopus Resource Center, European Xenopus Resource
Center, Xenopus Express)\r\nand our funding sources: U.S. National Science Foundation
(NSF) Grant Number IOS 2110086\r\n(D.B.K., L.B.S., M.A.T., A.Y., and H.T.C.); United
States-Israel Binational Science Foundation\r\n(BSF) Grant Number 2020702 (M.S.-I.);
NSF Award Number 1645105 (G.J.G., M.E.H.); FTI\r\nStrategy Lower Austria Dissertation
Grant Number FTI21-D-046 (D.V.); Horizon Europe ERC\r\nStarting Grant Number 101041551
(L.B.S.); NIH grant number R35GM146973 (M.A.T.); Rita Allen\r\nFoundation award
number GA_032522_FE (M.A.T.); European Molecular Biology Organization\r\nLong-Term
Fellowship ALTF 874-2021 (A.D.); National Science Foundation Graduate Research\r\nFellowship
DGE 2036197 (E.C.J.B.); NIH grant number P40OD010997 (M.E.H)."
article_processing_charge: No
author:
- first_name: Eliza C.B.
full_name: Jaeger, Eliza C.B.
last_name: Jaeger
- first_name: David
full_name: Vijatovic, David
id: cf391e77-ec3c-11ea-a124-d69323410b58
last_name: Vijatovic
- first_name: Astrid
full_name: Deryckere, Astrid
last_name: Deryckere
- first_name: Nikol
full_name: Zorin, Nikol
last_name: Zorin
- first_name: Akemi L.
full_name: Nguyen, Akemi L.
last_name: Nguyen
- first_name: Georgiy
full_name: Ivanian, Georgiy
id: eaf2b366-cfd1-11ee-bbdf-c8790f800a05
last_name: Ivanian
- first_name: Jamie
full_name: Woych, Jamie
last_name: Woych
- first_name: Rebecca C
full_name: Arnold, Rebecca C
id: d6cce458-14c9-11ed-a755-c1c8fc6fde6f
last_name: Arnold
- first_name: Alonso
full_name: Ortega Gurrola, Alonso
last_name: Ortega Gurrola
- first_name: Arik
full_name: Shvartsman, Arik
last_name: Shvartsman
- first_name: Francesca
full_name: Barbieri, Francesca
id: a9492887-8972-11ed-ae7b-bfae10998254
last_name: Barbieri
- first_name: Florina-Alexandra
full_name: Toma, Florina-Alexandra
id: 85dd99f2-15b2-11ec-abd3-d1ae4d57f3b5
last_name: Toma
- first_name: Gary J.
full_name: Gorbsky, Gary J.
last_name: Gorbsky
- first_name: Marko E.
full_name: Horb, Marko E.
last_name: Horb
- first_name: Hollis T.
full_name: Cline, Hollis T.
last_name: Cline
- first_name: Timothy F.
full_name: Shay, Timothy F.
last_name: Shay
- first_name: Darcy B.
full_name: Kelley, Darcy B.
last_name: Kelley
- first_name: Ayako
full_name: Yamaguchi, Ayako
last_name: Yamaguchi
- first_name: Mark
full_name: Shein-Idelson, Mark
last_name: Shein-Idelson
- first_name: Maria Antonietta
full_name: Tosches, Maria Antonietta
last_name: Tosches
- first_name: Lora Beatrice Jaeger
full_name: Sweeney, Lora Beatrice Jaeger
id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
last_name: Sweeney
orcid: 0000-0001-9242-5601
citation:
ama: Jaeger ECB, Vijatovic D, Deryckere A, et al. Adeno-associated viral tools to
trace neural development and connectivity across amphibians. bioRxiv. doi:10.1101/2024.02.15.580289
apa: Jaeger, E. C. B., Vijatovic, D., Deryckere, A., Zorin, N., Nguyen, A. L., Ivanian,
G., … Sweeney, L. B. (n.d.). Adeno-associated viral tools to trace neural development
and connectivity across amphibians. bioRxiv. https://doi.org/10.1101/2024.02.15.580289
chicago: Jaeger, Eliza C.B., David Vijatovic, Astrid Deryckere, Nikol Zorin, Akemi
L. Nguyen, Georgiy Ivanian, Jamie Woych, et al. “Adeno-Associated Viral Tools
to Trace Neural Development and Connectivity across Amphibians.” BioRxiv,
n.d. https://doi.org/10.1101/2024.02.15.580289.
ieee: E. C. B. Jaeger et al., “Adeno-associated viral tools to trace neural
development and connectivity across amphibians,” bioRxiv. .
ista: Jaeger ECB, Vijatovic D, Deryckere A, Zorin N, Nguyen AL, Ivanian G, Woych
J, Arnold RC, Ortega Gurrola A, Shvartsman A, Barbieri F, Toma F-A, Gorbsky GJ,
Horb ME, Cline HT, Shay TF, Kelley DB, Yamaguchi A, Shein-Idelson M, Tosches MA,
Sweeney LB. Adeno-associated viral tools to trace neural development and connectivity
across amphibians. bioRxiv, 10.1101/2024.02.15.580289.
mla: Jaeger, Eliza C. B., et al. “Adeno-Associated Viral Tools to Trace Neural Development
and Connectivity across Amphibians.” BioRxiv, doi:10.1101/2024.02.15.580289.
short: E.C.B. Jaeger, D. Vijatovic, A. Deryckere, N. Zorin, A.L. Nguyen, G. Ivanian,
J. Woych, R.C. Arnold, A. Ortega Gurrola, A. Shvartsman, F. Barbieri, F.-A. Toma,
G.J. Gorbsky, M.E. Horb, H.T. Cline, T.F. Shay, D.B. Kelley, A. Yamaguchi, M.
Shein-Idelson, M.A. Tosches, L.B. Sweeney, BioRxiv (n.d.).
date_created: 2024-02-20T09:20:32Z
date_published: 2024-02-16T00:00:00Z
date_updated: 2024-02-20T09:34:25Z
day: '16'
department:
- _id: LoSw
- _id: MaDe
- _id: GaNo
doi: 10.1101/2024.02.15.580289
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2024.02.15.580289
month: '02'
oa: 1
oa_version: Preprint
project:
- _id: bd73af52-d553-11ed-ba76-912049f0ac7a
grant_number: FTI21-D-046
name: Entwicklung und Funktion der V1 Interneuronen vom Schwimmen zum Laufen während
der Metamorphose von Xenopus
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
grant_number: '101041551'
name: Development and Evolution of Tetrapod Motor Circuits
publication: bioRxiv
publication_status: submitted
status: public
title: Adeno-associated viral tools to trace neural development and connectivity across
amphibians
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_id: '14443'
abstract:
- lang: eng
text: "Importance Climate change, pollution, urbanization, socioeconomic inequality,
and psychosocial effects of the COVID-19 pandemic have caused massive changes
in environmental conditions that affect brain health during the life span, both
on a population level as well as on the level of the individual. How these environmental
factors influence the brain, behavior, and mental illness is not well known.\r\nObservations
\ A research strategy enabling population neuroscience to contribute to identify
brain mechanisms underlying environment-related mental illness by leveraging innovative
enrichment tools for data federation, geospatial observation, climate and pollution
measures, digital health, and novel data integration techniques is described.
This strategy can inform innovative treatments that target causal cognitive and
molecular mechanisms of mental illness related to the environment. An example
is presented of the environMENTAL Project that is leveraging federated cohort
data of over 1.5 million European citizens and patients enriched with deep phenotyping
data from large-scale behavioral neuroimaging cohorts to identify brain mechanisms
related to environmental adversity underlying symptoms of depression, anxiety,
stress, and substance misuse.\r\nConclusions and Relevance This research will
lead to the development of objective biomarkers and evidence-based interventions
that will significantly improve outcomes of environment-related mental illness."
article_processing_charge: No
article_type: review
author:
- first_name: Gunter
full_name: Schumann, Gunter
last_name: Schumann
- first_name: Ole A.
full_name: Andreassen, Ole A.
last_name: Andreassen
- first_name: Tobias
full_name: Banaschewski, Tobias
last_name: Banaschewski
- first_name: Vince D.
full_name: Calhoun, Vince D.
last_name: Calhoun
- first_name: Nicholas
full_name: Clinton, Nicholas
last_name: Clinton
- first_name: Sylvane
full_name: Desrivieres, Sylvane
last_name: Desrivieres
- first_name: Ragnhild Eek
full_name: Brandlistuen, Ragnhild Eek
last_name: Brandlistuen
- first_name: Jianfeng
full_name: Feng, Jianfeng
last_name: Feng
- first_name: Soeren
full_name: Hese, Soeren
last_name: Hese
- first_name: Esther
full_name: Hitchen, Esther
last_name: Hitchen
- first_name: Per
full_name: Hoffmann, Per
last_name: Hoffmann
- first_name: Tianye
full_name: Jia, Tianye
last_name: Jia
- first_name: Viktor
full_name: Jirsa, Viktor
last_name: Jirsa
- first_name: Andre F.
full_name: Marquand, Andre F.
last_name: Marquand
- first_name: Frauke
full_name: Nees, Frauke
last_name: Nees
- first_name: Markus M.
full_name: Nöthen, Markus M.
last_name: Nöthen
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Elli
full_name: Polemiti, Elli
last_name: Polemiti
- first_name: Markus
full_name: Ralser, Markus
last_name: Ralser
- first_name: Michael
full_name: Rapp, Michael
last_name: Rapp
- first_name: Kerstin
full_name: Schepanski, Kerstin
last_name: Schepanski
- first_name: Tamara
full_name: Schikowski, Tamara
last_name: Schikowski
- first_name: Mel
full_name: Slater, Mel
last_name: Slater
- first_name: Peter
full_name: Sommer, Peter
last_name: Sommer
- first_name: Bernd Carsten
full_name: Stahl, Bernd Carsten
last_name: Stahl
- first_name: Paul M.
full_name: Thompson, Paul M.
last_name: Thompson
- first_name: Sven
full_name: Twardziok, Sven
last_name: Twardziok
- first_name: Dennis
full_name: Van Der Meer, Dennis
last_name: Van Der Meer
- first_name: Henrik
full_name: Walter, Henrik
last_name: Walter
- first_name: Lars
full_name: Westlye, Lars
last_name: Westlye
citation:
ama: 'Schumann G, Andreassen OA, Banaschewski T, et al. Addressing global environmental
challenges to mental health using population neuroscience: A review. JAMA Psychiatry.
2023;80(10):1066-1074. doi:10.1001/jamapsychiatry.2023.2996'
apa: 'Schumann, G., Andreassen, O. A., Banaschewski, T., Calhoun, V. D., Clinton,
N., Desrivieres, S., … Westlye, L. (2023). Addressing global environmental challenges
to mental health using population neuroscience: A review. JAMA Psychiatry.
American Medical Association. https://doi.org/10.1001/jamapsychiatry.2023.2996'
chicago: 'Schumann, Gunter, Ole A. Andreassen, Tobias Banaschewski, Vince D. Calhoun,
Nicholas Clinton, Sylvane Desrivieres, Ragnhild Eek Brandlistuen, et al. “Addressing
Global Environmental Challenges to Mental Health Using Population Neuroscience:
A Review.” JAMA Psychiatry. American Medical Association, 2023. https://doi.org/10.1001/jamapsychiatry.2023.2996.'
ieee: 'G. Schumann et al., “Addressing global environmental challenges to
mental health using population neuroscience: A review,” JAMA Psychiatry,
vol. 80, no. 10. American Medical Association, pp. 1066–1074, 2023.'
ista: 'Schumann G, Andreassen OA, Banaschewski T, Calhoun VD, Clinton N, Desrivieres
S, Brandlistuen RE, Feng J, Hese S, Hitchen E, Hoffmann P, Jia T, Jirsa V, Marquand
AF, Nees F, Nöthen MM, Novarino G, Polemiti E, Ralser M, Rapp M, Schepanski K,
Schikowski T, Slater M, Sommer P, Stahl BC, Thompson PM, Twardziok S, Van Der
Meer D, Walter H, Westlye L. 2023. Addressing global environmental challenges
to mental health using population neuroscience: A review. JAMA Psychiatry. 80(10),
1066–1074.'
mla: 'Schumann, Gunter, et al. “Addressing Global Environmental Challenges to Mental
Health Using Population Neuroscience: A Review.” JAMA Psychiatry, vol.
80, no. 10, American Medical Association, 2023, pp. 1066–74, doi:10.1001/jamapsychiatry.2023.2996.'
short: G. Schumann, O.A. Andreassen, T. Banaschewski, V.D. Calhoun, N. Clinton,
S. Desrivieres, R.E. Brandlistuen, J. Feng, S. Hese, E. Hitchen, P. Hoffmann,
T. Jia, V. Jirsa, A.F. Marquand, F. Nees, M.M. Nöthen, G. Novarino, E. Polemiti,
M. Ralser, M. Rapp, K. Schepanski, T. Schikowski, M. Slater, P. Sommer, B.C. Stahl,
P.M. Thompson, S. Twardziok, D. Van Der Meer, H. Walter, L. Westlye, JAMA Psychiatry
80 (2023) 1066–1074.
date_created: 2023-10-22T22:01:14Z
date_published: 2023-10-01T00:00:00Z
date_updated: 2023-10-31T12:17:20Z
day: '01'
department:
- _id: GaNo
doi: 10.1001/jamapsychiatry.2023.2996
external_id:
pmid:
- '37610741'
intvolume: ' 80'
issue: '10'
language:
- iso: eng
month: '10'
oa_version: None
page: 1066-1074
pmid: 1
publication: JAMA Psychiatry
publication_identifier:
eissn:
- 2168-6238
publication_status: published
publisher: American Medical Association
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Addressing global environmental challenges to mental health using population
neuroscience: A review'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 80
year: '2023'
...
---
_id: '13168'
abstract:
- lang: eng
text: Urban-living individuals are exposed to many environmental factors that may
combine and interact to influence mental health. While individual factors of an
urban environment have been investigated in isolation, no attempt has been made
to model how complex, real-life exposure to living in the city relates to brain
and mental health, and how this is moderated by genetic factors. Using the data
of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation
analyses to investigate the relationships between urban environments and psychiatric
symptoms. We found an environmental profile of social deprivation, air pollution,
street network and urban land-use density that was positively correlated with
an affective symptom group (r = 0.22, Pperm < 0.001), mediated by brain volume
differences consistent with reward processing, and moderated by genes enriched
for stress response, including CRHR1, explaining 2.01% of the variance in brain
volume differences. Protective factors such as greenness and generous destination
accessibility were negatively correlated with an anxiety symptom group (r = 0.10,
Pperm < 0.001), mediated by brain regions necessary for emotion regulation and
moderated by EXD3, explaining 1.65% of the variance. The third urban environmental
profile was correlated with an emotional instability symptom group (r = 0.03,
Pperm < 0.001). Our findings suggest that different environmental profiles of
urban living may influence specific psychiatric symptom groups through distinct
neurobiological pathways.
acknowledgement: This work received support from the European Union-funded Horizon
Europe project ‘environMENTAL’ (no. 101057429 to G.S., A.M. and M.M.N.) and cofunding
by UK Research and Innovation under the UK Government’s Horizon Europe funding guarantee
(nos. 10041392 and 10038599) for study design and data analysis; the Horizon 2020-funded
European Research Council Advanced Grant ‘STRATIFY’ (no. 695313 to G.S. for study
design and data analysis); the Human Brain Project (HBP SGA3, no. 945539 to G.S.
for study design and data analysis); the National Institutes of Health (grant no.
R01DA049238 to G.S. for study design and data analysis); the German Research Foundation
(COPE; grant no. 675346 to G.S. for study design and data analysis); the National
Natural Science Foundation of China (grant no. 82001797 to J.X., grant no. 82030053
to C.Y., grant no. 82202093 to J.T. and grant no. 82150710554 to G.S. for study
design, data analysis and preparation of the manuscript); National Key Research
and Development Program of China (grant no. 2018YFC1314301 to C.Y. for study design
and data analysis); Tianjin Applied Basic Research Diversified Investment Foundation
(grant no. 21JCYBJC01360 to J.X. for study design and data analysis); Tianjin Health
Technology Project (grant no. TJWJ2021QN002 to J.X. for preparation of the manuscript);
Science & Technology Development Fund of the Tianjin Education Commission for Higher
Education (grant no. 2019KJ195 to J.X. for preparation of the manuscript); the Tianjin
Medical University ‘Clinical Talent Training 123 Climbing Plan’ to J.X. for the
preparation of the manuscript; Tianjin Key Medical Discipline (Specialty) Construction
Project (grant no. TJYXZDXK-001A to C.Y. for preparation of the manuscript); the
National Key R&D Program of China (grant no. 2022YFE0209400 to L.Y. for study design
and data analysis); the Tsinghua University Initiative Scientific Research Program
(grant no. 2021Z11GHX002 to L.Y. for study design and data analysis); the National
Key Scientific and Technological Infrastructure Project ‘Earth System Science Numerical
Simulator Facility’ (EarthLab to L.Y. for study design and data analysis); the Chinese
National High-end Foreign Expert Recruitment Plan to G.S.; and the Alexander von
Humboldt Foundation to G.S. for study design and data analysis.
article_processing_charge: No
article_type: original
author:
- first_name: Jiayuan
full_name: Xu, Jiayuan
last_name: Xu
- first_name: Nana
full_name: Liu, Nana
last_name: Liu
- first_name: Elli
full_name: Polemiti, Elli
last_name: Polemiti
- first_name: Liliana
full_name: Garcia-Mondragon, Liliana
last_name: Garcia-Mondragon
- first_name: Jie
full_name: Tang, Jie
last_name: Tang
- first_name: Xiaoxuan
full_name: Liu, Xiaoxuan
last_name: Liu
- first_name: Tristram
full_name: Lett, Tristram
last_name: Lett
- first_name: Le
full_name: Yu, Le
last_name: Yu
- first_name: Markus M.
full_name: Nöthen, Markus M.
last_name: Nöthen
- first_name: Jianfeng
full_name: Feng, Jianfeng
last_name: Feng
- first_name: Chunshui
full_name: Yu, Chunshui
last_name: Yu
- first_name: Andre
full_name: Marquand, Andre
last_name: Marquand
- first_name: Gunter
full_name: Schumann, Gunter
last_name: Schumann
- first_name: Henrik
full_name: Walter, Henrik
last_name: Walter
- first_name: Andreas
full_name: Heinz, Andreas
last_name: Heinz
- first_name: Markus
full_name: Ralser, Markus
last_name: Ralser
- first_name: Sven
full_name: Twardziok, Sven
last_name: Twardziok
- first_name: Nilakshi
full_name: Vaidya, Nilakshi
last_name: Vaidya
- first_name: Emin
full_name: Serin, Emin
last_name: Serin
- first_name: Marcel
full_name: Jentsch, Marcel
last_name: Jentsch
- first_name: Esther
full_name: Hitchen, Esther
last_name: Hitchen
- first_name: Roland
full_name: Eils, Roland
last_name: Eils
- first_name: Ulrike Helene
full_name: Taron, Ulrike Helene
last_name: Taron
- first_name: Tatjana
full_name: Schütz, Tatjana
last_name: Schütz
- first_name: Kerstin
full_name: Schepanski, Kerstin
last_name: Schepanski
- first_name: Jamie
full_name: Banks, Jamie
last_name: Banks
- first_name: Tobias
full_name: Banaschewski, Tobias
last_name: Banaschewski
- first_name: Karina
full_name: Jansone, Karina
last_name: Jansone
- first_name: Nina
full_name: Christmann, Nina
last_name: Christmann
- first_name: Andreas
full_name: Meyer-Lindenberg, Andreas
last_name: Meyer-Lindenberg
- first_name: Heike
full_name: Tost, Heike
last_name: Tost
- first_name: Nathalie
full_name: Holz, Nathalie
last_name: Holz
- first_name: Emanuel
full_name: Schwarz, Emanuel
last_name: Schwarz
- first_name: Argyris
full_name: Stringaris, Argyris
last_name: Stringaris
- first_name: Maja
full_name: Neidhart, Maja
last_name: Neidhart
- first_name: Frauke
full_name: Nees, Frauke
last_name: Nees
- first_name: Sebastian
full_name: Siehl, Sebastian
last_name: Siehl
- first_name: Ole
full_name: A. Andreassen, Ole
last_name: A. Andreassen
- first_name: Lars
full_name: T. Westlye, Lars
last_name: T. Westlye
- first_name: Dennis
full_name: Van Der Meer, Dennis
last_name: Van Der Meer
- first_name: Sara
full_name: Fernandez, Sara
last_name: Fernandez
- first_name: Rikka
full_name: Kjelkenes, Rikka
last_name: Kjelkenes
- first_name: Helga
full_name: Ask, Helga
last_name: Ask
- first_name: Michael
full_name: Rapp, Michael
last_name: Rapp
- first_name: Mira
full_name: Tschorn, Mira
last_name: Tschorn
- first_name: Sarah Jane
full_name: Böttger, Sarah Jane
last_name: Böttger
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Lena
full_name: Marr, Lena
id: 4406F586-F248-11E8-B48F-1D18A9856A87
last_name: Marr
- first_name: Mel
full_name: Slater, Mel
last_name: Slater
- first_name: Guillem Feixas
full_name: Viapiana, Guillem Feixas
last_name: Viapiana
- first_name: Francisco Eiroa
full_name: Orosa, Francisco Eiroa
last_name: Orosa
- first_name: Jaime
full_name: Gallego, Jaime
last_name: Gallego
- first_name: Alvaro
full_name: Pastor, Alvaro
last_name: Pastor
- first_name: Andreas
full_name: Forstner, Andreas
last_name: Forstner
- first_name: Per
full_name: Hoffmann, Per
last_name: Hoffmann
- first_name: Markus
full_name: M. Nöthen, Markus
last_name: M. Nöthen
- first_name: Andreas
full_name: J. Forstner, Andreas
last_name: J. Forstner
- first_name: Isabelle
full_name: Claus, Isabelle
last_name: Claus
- first_name: Abbi
full_name: Miller, Abbi
last_name: Miller
- first_name: Stefanie
full_name: Heilmann-Heimbach, Stefanie
last_name: Heilmann-Heimbach
- first_name: Peter
full_name: Sommer, Peter
last_name: Sommer
- first_name: Mona
full_name: Boye, Mona
last_name: Boye
- first_name: Johannes
full_name: Wilbertz, Johannes
last_name: Wilbertz
- first_name: Karen
full_name: Schmitt, Karen
last_name: Schmitt
- first_name: Viktor
full_name: Jirsa, Viktor
last_name: Jirsa
- first_name: Spase
full_name: Petkoski, Spase
last_name: Petkoski
- first_name: Séverine
full_name: Pitel, Séverine
last_name: Pitel
- first_name: Lisa
full_name: Otten, Lisa
last_name: Otten
- first_name: Anastasios Polykarpos
full_name: Athanasiadis, Anastasios Polykarpos
last_name: Athanasiadis
- first_name: Charlie
full_name: Pearmund, Charlie
last_name: Pearmund
- first_name: Bernhard
full_name: Spanlang, Bernhard
last_name: Spanlang
- first_name: Elena
full_name: Alvarez, Elena
last_name: Alvarez
- first_name: Mavi
full_name: Sanchez, Mavi
last_name: Sanchez
- first_name: Arantxa
full_name: Giner, Arantxa
last_name: Giner
- first_name: Sören
full_name: Hese, Sören
last_name: Hese
- first_name: Paul
full_name: Renner, Paul
last_name: Renner
- first_name: Tianye
full_name: Jia, Tianye
last_name: Jia
- first_name: Yanting
full_name: Gong, Yanting
last_name: Gong
- first_name: Yunman
full_name: Xia, Yunman
last_name: Xia
- first_name: Xiao
full_name: Chang, Xiao
last_name: Chang
- first_name: Vince
full_name: Calhoun, Vince
last_name: Calhoun
- first_name: Jingyu
full_name: Liu, Jingyu
last_name: Liu
- first_name: Paul
full_name: Thompson, Paul
last_name: Thompson
- first_name: Nicholas
full_name: Clinton, Nicholas
last_name: Clinton
- first_name: Sylvane
full_name: Desrivieres, Sylvane
last_name: Desrivieres
- first_name: Allan
full_name: H. Young, Allan
last_name: H. Young
- first_name: Bernd
full_name: Stahl, Bernd
last_name: Stahl
- first_name: George
full_name: Ogoh, George
last_name: Ogoh
citation:
ama: Xu J, Liu N, Polemiti E, et al. Effects of urban living environments on mental
health in adults. Nature Medicine. 2023;29:1456-1467. doi:10.1038/s41591-023-02365-w
apa: Xu, J., Liu, N., Polemiti, E., Garcia-Mondragon, L., Tang, J., Liu, X., … Ogoh,
G. (2023). Effects of urban living environments on mental health in adults. Nature
Medicine. Springer Nature. https://doi.org/10.1038/s41591-023-02365-w
chicago: Xu, Jiayuan, Nana Liu, Elli Polemiti, Liliana Garcia-Mondragon, Jie Tang,
Xiaoxuan Liu, Tristram Lett, et al. “Effects of Urban Living Environments on Mental
Health in Adults.” Nature Medicine. Springer Nature, 2023. https://doi.org/10.1038/s41591-023-02365-w.
ieee: J. Xu et al., “Effects of urban living environments on mental health
in adults,” Nature Medicine, vol. 29. Springer Nature, pp. 1456–1467, 2023.
ista: Xu J, Liu N, Polemiti E, Garcia-Mondragon L, Tang J, Liu X, Lett T, Yu L,
Nöthen MM, Feng J, Yu C, Marquand A, Schumann G, Walter H, Heinz A, Ralser M,
Twardziok S, Vaidya N, Serin E, Jentsch M, Hitchen E, Eils R, Taron UH, Schütz
T, Schepanski K, Banks J, Banaschewski T, Jansone K, Christmann N, Meyer-Lindenberg
A, Tost H, Holz N, Schwarz E, Stringaris A, Neidhart M, Nees F, Siehl S, A. Andreassen
O, T. Westlye L, Van Der Meer D, Fernandez S, Kjelkenes R, Ask H, Rapp M, Tschorn
M, Böttger SJ, Novarino G, Marr L, Slater M, Viapiana GF, Orosa FE, Gallego J,
Pastor A, Forstner A, Hoffmann P, M. Nöthen M, J. Forstner A, Claus I, Miller
A, Heilmann-Heimbach S, Sommer P, Boye M, Wilbertz J, Schmitt K, Jirsa V, Petkoski
S, Pitel S, Otten L, Athanasiadis AP, Pearmund C, Spanlang B, Alvarez E, Sanchez
M, Giner A, Hese S, Renner P, Jia T, Gong Y, Xia Y, Chang X, Calhoun V, Liu J,
Thompson P, Clinton N, Desrivieres S, H. Young A, Stahl B, Ogoh G. 2023. Effects
of urban living environments on mental health in adults. Nature Medicine. 29,
1456–1467.
mla: Xu, Jiayuan, et al. “Effects of Urban Living Environments on Mental Health
in Adults.” Nature Medicine, vol. 29, Springer Nature, 2023, pp. 1456–67,
doi:10.1038/s41591-023-02365-w.
short: J. Xu, N. Liu, E. Polemiti, L. Garcia-Mondragon, J. Tang, X. Liu, T. Lett,
L. Yu, M.M. Nöthen, J. Feng, C. Yu, A. Marquand, G. Schumann, H. Walter, A. Heinz,
M. Ralser, S. Twardziok, N. Vaidya, E. Serin, M. Jentsch, E. Hitchen, R. Eils,
U.H. Taron, T. Schütz, K. Schepanski, J. Banks, T. Banaschewski, K. Jansone, N.
Christmann, A. Meyer-Lindenberg, H. Tost, N. Holz, E. Schwarz, A. Stringaris,
M. Neidhart, F. Nees, S. Siehl, O. A. Andreassen, L. T. Westlye, D. Van Der Meer,
S. Fernandez, R. Kjelkenes, H. Ask, M. Rapp, M. Tschorn, S.J. Böttger, G. Novarino,
L. Marr, M. Slater, G.F. Viapiana, F.E. Orosa, J. Gallego, A. Pastor, A. Forstner,
P. Hoffmann, M. M. Nöthen, A. J. Forstner, I. Claus, A. Miller, S. Heilmann-Heimbach,
P. Sommer, M. Boye, J. Wilbertz, K. Schmitt, V. Jirsa, S. Petkoski, S. Pitel,
L. Otten, A.P. Athanasiadis, C. Pearmund, B. Spanlang, E. Alvarez, M. Sanchez,
A. Giner, S. Hese, P. Renner, T. Jia, Y. Gong, Y. Xia, X. Chang, V. Calhoun, J.
Liu, P. Thompson, N. Clinton, S. Desrivieres, A. H. Young, B. Stahl, G. Ogoh,
Nature Medicine 29 (2023) 1456–1467.
date_created: 2023-06-25T22:00:46Z
date_published: 2023-06-15T00:00:00Z
date_updated: 2023-12-13T11:25:55Z
day: '15'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1038/s41591-023-02365-w
external_id:
isi:
- '001013172700001'
file:
- access_level: open_access
checksum: bcd3225b2731c3442fa98987fd3bd46d
content_type: application/pdf
creator: dernst
date_created: 2023-06-26T10:15:44Z
date_updated: 2023-06-26T10:15:44Z
file_id: '13171'
file_name: 2023_NatureMedicine_Xu.pdf
file_size: 7365360
relation: main_file
success: 1
file_date_updated: 2023-06-26T10:15:44Z
has_accepted_license: '1'
intvolume: ' 29'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '06'
oa: 1
oa_version: Published Version
page: 1456-1467
publication: Nature Medicine
publication_identifier:
eissn:
- 1546-170X
issn:
- 1078-8956
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Effects of urban living environments on mental health in adults
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 29
year: '2023'
...
---
_id: '14455'
acknowledgement: The author(s) declare that financial support was received for the
research, authorship, and/or publication of this article. This work has been partially
supported by Italian Ministry of Health Grant RC2023 (and the 5 × 1,000 voluntary
contributions). The authors thank the children and their families with whom they
work daily.
article_number: '1287879'
article_processing_charge: Yes
article_type: letter_note
author:
- first_name: Antonio
full_name: Narzisi, Antonio
last_name: Narzisi
- first_name: Alycia
full_name: Halladay, Alycia
last_name: Halladay
- first_name: Gabriele
full_name: Masi, Gabriele
last_name: Masi
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Catherine
full_name: Lord, Catherine
last_name: Lord
citation:
ama: 'Narzisi A, Halladay A, Masi G, Novarino G, Lord C. Tempering expectations:
Considerations on the current state of stem cells therapy for autism treatment.
Frontiers in Psychiatry. 2023;14. doi:10.3389/fpsyt.2023.1287879'
apa: 'Narzisi, A., Halladay, A., Masi, G., Novarino, G., & Lord, C. (2023).
Tempering expectations: Considerations on the current state of stem cells therapy
for autism treatment. Frontiers in Psychiatry. Frontiers. https://doi.org/10.3389/fpsyt.2023.1287879'
chicago: 'Narzisi, Antonio, Alycia Halladay, Gabriele Masi, Gaia Novarino, and Catherine
Lord. “Tempering Expectations: Considerations on the Current State of Stem Cells
Therapy for Autism Treatment.” Frontiers in Psychiatry. Frontiers, 2023.
https://doi.org/10.3389/fpsyt.2023.1287879.'
ieee: 'A. Narzisi, A. Halladay, G. Masi, G. Novarino, and C. Lord, “Tempering expectations:
Considerations on the current state of stem cells therapy for autism treatment,”
Frontiers in Psychiatry, vol. 14. Frontiers, 2023.'
ista: 'Narzisi A, Halladay A, Masi G, Novarino G, Lord C. 2023. Tempering expectations:
Considerations on the current state of stem cells therapy for autism treatment.
Frontiers in Psychiatry. 14, 1287879.'
mla: 'Narzisi, Antonio, et al. “Tempering Expectations: Considerations on the Current
State of Stem Cells Therapy for Autism Treatment.” Frontiers in Psychiatry,
vol. 14, 1287879, Frontiers, 2023, doi:10.3389/fpsyt.2023.1287879.'
short: A. Narzisi, A. Halladay, G. Masi, G. Novarino, C. Lord, Frontiers in Psychiatry
14 (2023).
date_created: 2023-10-29T23:01:16Z
date_published: 2023-10-03T00:00:00Z
date_updated: 2023-12-13T13:06:07Z
day: '03'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3389/fpsyt.2023.1287879
external_id:
isi:
- '001084841700001'
pmid:
- '37854442'
file:
- access_level: open_access
checksum: 0a76373e9a4c0fc199f80380de257e86
content_type: application/pdf
creator: dernst
date_created: 2023-10-30T12:48:40Z
date_updated: 2023-10-30T12:48:40Z
file_id: '14468'
file_name: 2023_FrontiersPsychiatry_Narzisi.pdf
file_size: 147878
relation: main_file
success: 1
file_date_updated: 2023-10-30T12:48:40Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Psychiatry
publication_identifier:
eissn:
- 1664-0640
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Tempering expectations: Considerations on the current state of stem cells
therapy for autism treatment'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2023'
...
---
_id: '13267'
abstract:
- lang: eng
text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual
synapse level would create opportunities for decoding the dynamics and structure–function
relationships of the brain’s complex and dense information processing network;
however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise
ratio and prohibitive light burden in optical imaging, whereas electron microscopy
is inherently static. Here we solved these challenges by developing an integrated
optical/machine-learning technology, LIONESS (live information-optimized nanoscopy
enabling saturated segmentation). This leverages optical modifications to stimulated
emission depletion microscopy in comprehensively, extracellularly labeled tissue
and previous information on sample structure via machine learning to simultaneously
achieve isotropic super-resolution, high signal-to-noise ratio and compatibility
with living tissue. This allows dense deep-learning-based instance segmentation
and 3D reconstruction at a synapse level, incorporating molecular, activity and
morphodynamic information. LIONESS opens up avenues for studying the dynamic functional
(nano-)architecture of living brain tissue.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: E-Lib
- _id: LifeSc
- _id: M-Shop
acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance
and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata
for hardware control support and M. Cunha dos Santos for initial exploration of
software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt,
S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L.
Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We
acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and
optics, preclinical, library and laboratory support facilities and by the Miba machine
shop. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.)
and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung
NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D.
and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska
Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research
and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE
(B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.);
and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research
Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development
grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship
no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier
Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science
Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)."
article_processing_charge: Yes
article_type: original
author:
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Eder
full_name: Miguel Villalba, Eder
id: 3FB91342-F248-11E8-B48F-1D18A9856A87
last_name: Miguel Villalba
orcid: 0000-0001-5665-0430
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Donglai
full_name: Wei, Donglai
last_name: Wei
- first_name: Zudi
full_name: Lin, Zudi
last_name: Lin
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Jakob
full_name: Troidl, Jakob
last_name: Troidl
- first_name: Johanna
full_name: Beyer, Johanna
last_name: Beyer
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Wiebke
full_name: Jahr, Wiebke
id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
last_name: Jahr
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Johannes
full_name: Broichhagen, Johannes
last_name: Broichhagen
- first_name: Seth G.N.
full_name: Grant, Seth G.N.
last_name: Grant
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Hanspeter
full_name: Pfister, Hanspeter
last_name: Pfister
- first_name: Bernd
full_name: Bickel, Bernd
id: 49876194-F248-11E8-B48F-1D18A9856A87
last_name: Bickel
orcid: 0000-0001-6511-9385
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction
of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6
apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D.,
Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain
tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6
chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik,
Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction
of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6.
ieee: P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain
tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.
ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson
J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen
J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense
4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.
mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain
Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6.
short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin,
J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri,
J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel,
J.G. Danzl, Nature Methods 20 (2023) 1256–1265.
date_created: 2023-07-23T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2024-01-10T08:37:48Z
day: '01'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
- _id: Bio
doi: 10.1038/s41592-023-01936-6
ec_funded: 1
external_id:
isi:
- '001025621500001'
pmid:
- '37429995'
intvolume: ' 20'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41592-023-01936-6
month: '08'
oa: 1
oa_version: Published Version
page: 1256-1265
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 24F9549A-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715767'
name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and
Modeling'
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 2668BFA0-B435-11E9-9278-68D0E5697425
grant_number: LT00057
name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration
publication: Nature Methods
publication_identifier:
eissn:
- 1548-7105
issn:
- 1548-7091
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/LIONESS
record:
- id: '12817'
relation: research_data
status: public
- id: '14770'
relation: shorter_version
status: public
scopus_import: '1'
status: public
title: Dense 4D nanoscale reconstruction of living brain tissue
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2023'
...
---
_id: '13107'
abstract:
- lang: eng
text: "Within the human body, the brain exhibits the highest rate of energy consumption
amongst all organs, with the majority of generated ATP being utilized to sustain
neuronal activity. Therefore, the metabolism of the mature cerebral cortex is
geared towards preserving metabolic homeostasis whilst generating significant
amounts of energy. This requires a precise interplay between diverse metabolic
pathways, spanning from a tissue-wide scale to the level of individual neurons.
Disturbances to this delicate metabolic equilibrium, such as those resulting from
maternal malnutrition\r\nor mutations affecting metabolic enzymes, often result
in neuropathological variants of neurodevelopment. For instance, mutations in
SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs),
have been associated with autism and microcephaly. However, despite recent progress
in the field, the extent of metabolic restructuring that occurs within the developing
brain and the corresponding alterations in nutrient demands during various critical
periods remain largely unknown. To investigate this, we performed metabolomic
profiling of the murine cerebral cortex to characterize the metabolic state of
the forebrain at different developmental stages. We found that the developing
cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites
displaying stage-specific changes. According to our observations, we determined
a distinct temporal period in postnatal development during which the cortex displays
heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model,
we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed
neuronal metabolic state across multiple developmental stages of corticogenesis.
We found that manipulating the levels of essential LNAAs in cortical neurons in
vivo affects one particular perinatal developmental period critical for cortical
network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous
alterations in neuronal lipid metabolism, excitability, and survival during this
particular time window. Although most of the effects of Slc7a5 deletion on neuronal
physiology are transient, derailment of these processes during this brief but
crucial window leads to long-term circuit dysfunction in mice. In conclusion,
out data indicate that the cerebral cortex undergoes significant metabolic reorganization
during development. This process involves the intricate integration of multiple
metabolic pathways to ensure optimal neuronal function throughout different developmental
stages. Our findings offer a paradigm for understanding how neurons synchronize
the expression of nutrient-related genes with their activity to allow proper brain
maturation. Further, our results demonstrate that disruptions in these precisely
calibrated metabolic processes during critical periods of brain development may
result in neuropathological outcomes in mice and in humans."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
citation:
ama: 'Knaus L. The metabolism of the developing brain : How large neutral amino
acids modulate perinatal neuronal excitability and survival. 2023. doi:10.15479/at:ista:13107'
apa: 'Knaus, L. (2023). The metabolism of the developing brain : How large neutral
amino acids modulate perinatal neuronal excitability and survival. Institute
of Science and Technology Austria. https://doi.org/10.15479/at:ista:13107'
chicago: 'Knaus, Lisa. “The Metabolism of the Developing Brain : How Large Neutral
Amino Acids Modulate Perinatal Neuronal Excitability and Survival.” Institute
of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13107.'
ieee: 'L. Knaus, “The metabolism of the developing brain : How large neutral amino
acids modulate perinatal neuronal excitability and survival,” Institute of Science
and Technology Austria, 2023.'
ista: 'Knaus L. 2023. The metabolism of the developing brain : How large neutral
amino acids modulate perinatal neuronal excitability and survival. Institute of
Science and Technology Austria.'
mla: 'Knaus, Lisa. The Metabolism of the Developing Brain : How Large Neutral
Amino Acids Modulate Perinatal Neuronal Excitability and Survival. Institute
of Science and Technology Austria, 2023, doi:10.15479/at:ista:13107.'
short: 'L. Knaus, The Metabolism of the Developing Brain : How Large Neutral Amino
Acids Modulate Perinatal Neuronal Excitability and Survival, Institute of Science
and Technology Austria, 2023.'
date_created: 2023-06-01T09:05:24Z
date_published: 2023-05-31T00:00:00Z
date_updated: 2024-02-07T08:03:33Z
day: '31'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaNo
doi: 10.15479/at:ista:13107
ec_funded: 1
file:
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date_created: 2023-06-01T13:48:41Z
date_updated: 2023-06-01T13:48:41Z
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file_size: 9309015
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language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '147'
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication_identifier:
issn:
- 2663 - 337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '12802'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: 'The metabolism of the developing brain : How large neutral amino acids modulate
perinatal neuronal excitability and survival'
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '12802'
abstract:
- lang: eng
text: Little is known about the critical metabolic changes that neural cells have
to undergo during development and how temporary shifts in this program can influence
brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5,
a transporter of metabolically essential large neutral amino acids (LNAAs), lead
to autism, we employed metabolomic profiling to study the metabolic states of
the cerebral cortex across different developmental stages. We found that the forebrain
undergoes significant metabolic remodeling throughout development, with certain
groups of metabolites showing stage-specific changes, but what are the consequences
of perturbing this metabolic program? By manipulating Slc7a5 expression in neural
cells, we found that the metabolism of LNAAs and lipids are interconnected in
the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state,
leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific
alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Freeman and V. Voronin for technical assistance, S. Deixler,
A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal
colony. We thank L. Andersen and J. Sonntag, who were involved in generating the
MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance
with the proteomic analysis, as well as the ISTA electron microscopy and Imaging
and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed
by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge
the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular
metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was
performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated
using Biorender.com. This work was supported by the Austrian Science Fund (FWF,
DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Daniel
full_name: Malzl, Daniel
last_name: Malzl
- first_name: Maria
full_name: Gerykova Bujalkova, Maria
last_name: Gerykova Bujalkova
- first_name: Mateja
full_name: Smogavec, Mateja
last_name: Smogavec
- first_name: Lena A.
full_name: Schwarz, Lena A.
last_name: Schwarz
- first_name: Sarah
full_name: Gorkiewicz, Sarah
id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
last_name: Gorkiewicz
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Christian
full_name: Knittl-Frank, Christian
last_name: Knittl-Frank
- first_name: Marianna
full_name: Tassinari, Marianna
id: 7af593f1-d44a-11ed-bf94-a3646a6bb35e
last_name: Tassinari
- first_name: Nuno
full_name: Maulide, Nuno
last_name: Maulide
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Jörg
full_name: Menche, Jörg
last_name: Menche
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal
neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037
apa: Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz,
L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal
excitability and survival. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037
chicago: Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova,
Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino
Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier,
2023. https://doi.org/10.1016/j.cell.2023.02.037.
ieee: L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal
excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25,
2023.
ista: Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA,
Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke
T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels
tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.
mla: Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal
Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25,
doi:10.1016/j.cell.2023.02.037.
short: L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A.
Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N.
Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.
date_created: 2023-04-05T08:15:40Z
date_published: 2023-04-27T00:00:00Z
date_updated: 2024-02-07T08:03:32Z
day: '27'
ddc:
- '570'
department:
- _id: SiHi
- _id: GaNo
doi: 10.1016/j.cell.2023.02.037
ec_funded: 1
external_id:
isi:
- '000991468700001'
file:
- access_level: open_access
checksum: 47e94fbe19e86505b429cb7a5b503ce6
content_type: application/pdf
creator: dernst
date_created: 2023-05-02T09:26:21Z
date_updated: 2023-05-02T09:26:21Z
file_id: '12889'
file_name: 2023_Cell_Knaus.pdf
file_size: 15712841
relation: main_file
success: 1
file_date_updated: 2023-05-02T09:26:21Z
has_accepted_license: '1'
intvolume: ' 186'
isi: 1
issue: '9'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 1950-1967.e25
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
publication: Cell
publication_identifier:
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/feed-them-or-lose-them/
record:
- id: '13107'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Large neutral amino acid levels tune perinatal neuronal excitability and survival
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 186
year: '2023'
...
---
_id: '14257'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
Erber for technical assistance; and M. Tomschik for support with obtaining human
samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
for computational support and hardware control. We are grateful to R. Shigemoto
and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
provided by S. Grant (University of Edinburgh). We acknowledge expert support by
Institute of Science and Technology Austria’s scientific computing, imaging and
optics, preclinical and lab support facilities and by the Miba machine shop and
library. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
(J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
(P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
(R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
European Union’s Horizon 2020 research and innovation programme, European Research
Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Romana
full_name: Höftberger, Romana
last_name: Höftberger
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer
Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.
ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter
to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology.
mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).
date_created: 2023-09-03T22:01:15Z
date_published: 2023-08-31T00:00:00Z
date_updated: 2024-02-21T12:18:18Z
day: '31'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
isi:
- '001065254200001'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41587-023-01911-8
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/CATS
record:
- id: '13126'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '12140'
abstract:
- lang: eng
text: Microglia are dynamic cells, constantly surveying their surroundings and interacting
with neurons and synapses. Indeed, a wealth of knowledge has revealed a critical
role of microglia in modulating synaptic transmission and plasticity in the developing
brain. In the past decade, novel pharmacological and genetic strategies have allowed
the acute removal of microglia, opening the possibility to explore and understand
the role of microglia also in the adult brain. In this review, we summarized and
discussed the contribution of microglia depletion strategies to the current understanding
of the role of microglia on synaptic function, learning and memory, and behavior
both in physiological and pathological conditions. We first described the available
microglia depletion methods highlighting their main strengths and weaknesses.
We then reviewed the impact of microglia depletion on structural and functional
synaptic plasticity. Next, we focused our analysis on the effects of microglia
depletion on behavior, including general locomotor activity, sensory perception,
motor function, sociability, learning and memory both in healthy animals and animal
models of disease. Finally, we integrated the findings from the reviewed studies
and discussed the emerging roles of microglia on the maintenance of synaptic function,
learning, memory strength and forgetfulness, and the implications of microglia
depletion in models of brain disease.
acknowledgement: "The write-up of the review was supported by Sapienza University
of Rome (Fondi di Ateneo, grant numbers #MA32117A7B698029 and #PH12017270934C3C
to SD), Regione Lazio (POR FSE 2014/20, grant number #19036AP000000019 to SD), Fulbright
2019 (grant number\r\n#FSP-P005556 to SD), Institute Pasteur Italia (Fondi Cenci
Bolognetti #363 to DR), and Network of European Funding for Neuroscience Research
(ERA-NET NEURON Transnational\r\nResearch Projects on Neurodevelopmental Disorders
2021, grant acronym #JTC2021-SHANKAstro to DR)."
article_number: '1022431'
article_processing_charge: No
article_type: original
author:
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Laura
full_name: Ferrucci, Laura
last_name: Ferrucci
- first_name: Azka
full_name: Khan, Azka
last_name: Khan
- first_name: Silvia
full_name: Di Angelantonio, Silvia
last_name: Di Angelantonio
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
- first_name: Ingrid
full_name: Reverte, Ingrid
last_name: Reverte
citation:
ama: Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I.
What microglia depletion approaches tell us about the role of microglia on synaptic
function and behavior. Frontiers in Cellular Neuroscience. 2022;16. doi:10.3389/fncel.2022.1022431
apa: Basilico, B., Ferrucci, L., Khan, A., Di Angelantonio, S., Ragozzino, D., &
Reverte, I. (2022). What microglia depletion approaches tell us about the role
of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience.
Frontiers Media. https://doi.org/10.3389/fncel.2022.1022431
chicago: Basilico, Bernadette, Laura Ferrucci, Azka Khan, Silvia Di Angelantonio,
Davide Ragozzino, and Ingrid Reverte. “What Microglia Depletion Approaches Tell
Us about the Role of Microglia on Synaptic Function and Behavior.” Frontiers
in Cellular Neuroscience. Frontiers Media, 2022. https://doi.org/10.3389/fncel.2022.1022431.
ieee: B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, and I.
Reverte, “What microglia depletion approaches tell us about the role of microglia
on synaptic function and behavior,” Frontiers in Cellular Neuroscience,
vol. 16. Frontiers Media, 2022.
ista: Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I.
2022. What microglia depletion approaches tell us about the role of microglia
on synaptic function and behavior. Frontiers in Cellular Neuroscience. 16, 1022431.
mla: Basilico, Bernadette, et al. “What Microglia Depletion Approaches Tell Us about
the Role of Microglia on Synaptic Function and Behavior.” Frontiers in Cellular
Neuroscience, vol. 16, 1022431, Frontiers Media, 2022, doi:10.3389/fncel.2022.1022431.
short: B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, I. Reverte,
Frontiers in Cellular Neuroscience 16 (2022).
date_created: 2023-01-12T12:04:50Z
date_published: 2022-11-04T00:00:00Z
date_updated: 2023-08-04T08:56:10Z
day: '04'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3389/fncel.2022.1022431
external_id:
isi:
- '000886526600001'
pmid:
- '36406752'
file:
- access_level: open_access
checksum: 84696213ecf99182c58a9f34b9ff2e23
content_type: application/pdf
creator: dernst
date_created: 2023-01-24T09:16:29Z
date_updated: 2023-01-24T09:16:29Z
file_id: '12352'
file_name: 2022_FrontiersNeuroscience_Basilico.pdf
file_size: 6399987
relation: main_file
success: 1
file_date_updated: 2023-01-24T09:16:29Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
keyword:
- Cellular and Molecular Neuroscience
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Cellular Neuroscience
publication_identifier:
issn:
- 1662-5102
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: What microglia depletion approaches tell us about the role of microglia on
synaptic function and behavior
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 16
year: '2022'
...
---
_id: '12174'
abstract:
- lang: eng
text: "Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety
of cellular membranes that acts as an ATP-dependent proton pump and plays a key
role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal
genes encode for a redundant set of subunits allowing the composition of diverse
V-ATPase complexes with specific properties and expression. Sixteen subunits have
been linked to human disease.\r\nHere we describe 26 patients harbouring 20 distinct
pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP
synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes:
6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures
included early lethal encephalopathies with rapidly progressive massive brain
atrophy, severe developmental epileptic encephalopathies and static intellectual
disability with epilepsy. The first clinical manifestation was early hypotonia,
in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies
in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic
encephalopathies failed to achieve any developmental, communicative or motor skills.
Less severe outcomes were observed in 23% of patients who, at a mean age of 10
years and 6 months, exhibited moderate intellectual disability, with independent
walking and variable epilepsy. None of the patients developed communicative language.
Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional
clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy
in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs.\r\n
\ Fibroblasts of two patients with developmental epileptic
encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased
organelle pH, consistent with lysosomal impairment and loss of V-ATPase function.
Fibroblasts of two patients with milder disease, exhibited a different phenotype
with increased Lysotracker staining, decreased organelle pH and no significant
modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes
in cellular extracts from four patients revealed discrete accumulation. Transmission
electron microscopy of fibroblasts of four patients with variable severity and
of induced pluripotent stem cell-derived neurons from two patients with developmental
epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic
material and lamellated membrane structures resembling phospholipids. Quantitative
assessment in induced pluripotent stem cell-derived neurons identified significantly
smaller lysosomes.\r\nATP6V1A-related encephalopathy represents a new paradigm
among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane
protein causing altered pH homeostasis. Its pathophysiology implies intracellular
accumulation of substrates whose composition remains unclear, and a combination
of developmental brain abnormalities and neurodegenerative changes established
during prenatal and early postanal development, whose severity is variably determined
by specific pathogenic variants."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
acknowledgement: "We thank all patients and family members for their participation
in this study. We thank Melanie Pieraks and Eva Reinthaler (Neurolentech, Austria)
for generating the human iPSC lines and\r\nfor performing quality checks. We thank
Vanessa Zheden and Daniel Gütl for their excellent technical support in the specimen
preparation for transmission electron microscopy and Flavia Leite for preparing
the lentiviruses. The support from Electron Microscopy Facility and Molecular Biology
Services at IST Austria is greatly acknowledged. We would like to thank Doctors
Jane Hurst and Richard Scott for their help in retrieving the detailed clinical
information of Patient 17. The research team acknowledges the support of the National
Institute for Health Research, through the Comprehensive Clinical Research Network.
See Supplementary Material for Undiagnosed Disease Network consortium details. Genetic
information on Patient 23 was made available through access to the data and findings
generated by the 100 000 Genomes\r\nProject; www.genomicsengland.co.uk (to K.L.).
\r\nThis work was supported by the EU 7th Framework Programme (FP7) under the project
DESIRE grant N602531 (to R.G.); the Regione Toscana under the Call for Health 2018
(grant\r\nDECODE-EE) (to R.G.); the ‘Brain Project’ by Fondazione Cassa di Risparmio
di Firenze (to R.G.); IRCCS Ospedale Policlinico San Martino 5×1000 and Ricerca
Corrente (to A.F. and F.B.). The European Reference Network (ERN) for rare and complex
epilepsies (EpiCARE) provided financial support for meetings organization. The DDD
study presents independent research commissioned by the Health Innovation Challenge
Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome
and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051).
The views expressed in this publication\r\nare those of the author(s) and not necessarily
those of Wellcome or the Department of Health. The study has UK Research Ethics
Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12
granted by the Republic of Ireland REC). This study makes use of DECIPHER (https://www.deciphergenomics.org),
which is funded by Wellcome. K.K.-S. was supported by the ISTplus fellowship. "
article_processing_charge: No
article_type: original
author:
- first_name: Renzo
full_name: Guerrini, Renzo
last_name: Guerrini
- first_name: Davide
full_name: Mei, Davide
last_name: Mei
- first_name: Margit Katalin
full_name: Szigeti, Margit Katalin
id: 44F4BDC0-F248-11E8-B48F-1D18A9856A87
last_name: Szigeti
orcid: 0000-0001-9500-8758
- first_name: Sara
full_name: Pepe, Sara
last_name: Pepe
- first_name: Mary Kay
full_name: Koenig, Mary Kay
last_name: Koenig
- first_name: Gretchen
full_name: Von Allmen, Gretchen
last_name: Von Allmen
- first_name: Megan T
full_name: Cho, Megan T
last_name: Cho
- first_name: Kimberly
full_name: McDonald, Kimberly
last_name: McDonald
- first_name: Janice
full_name: Baker, Janice
last_name: Baker
- first_name: Vikas
full_name: Bhambhani, Vikas
last_name: Bhambhani
- first_name: Zöe
full_name: Powis, Zöe
last_name: Powis
- first_name: Lance
full_name: Rodan, Lance
last_name: Rodan
- first_name: Rima
full_name: Nabbout, Rima
last_name: Nabbout
- first_name: Giulia
full_name: Barcia, Giulia
last_name: Barcia
- first_name: Jill A
full_name: Rosenfeld, Jill A
last_name: Rosenfeld
- first_name: Carlos A
full_name: Bacino, Carlos A
last_name: Bacino
- first_name: Cyril
full_name: Mignot, Cyril
last_name: Mignot
- first_name: Lillian H
full_name: Power, Lillian H
last_name: Power
- first_name: Catharine J
full_name: Harris, Catharine J
last_name: Harris
- first_name: Dragan
full_name: Marjanovic, Dragan
last_name: Marjanovic
- first_name: Rikke S
full_name: Møller, Rikke S
last_name: Møller
- first_name: Trine B
full_name: Hammer, Trine B
last_name: Hammer
- first_name: Riikka
full_name: Keski Filppula, Riikka
last_name: Keski Filppula
- first_name: Päivi
full_name: Vieira, Päivi
last_name: Vieira
- first_name: Clara
full_name: Hildebrandt, Clara
last_name: Hildebrandt
- first_name: Stephanie
full_name: Sacharow, Stephanie
last_name: Sacharow
- first_name: Luca
full_name: Maragliano, Luca
last_name: Maragliano
- first_name: Fabio
full_name: Benfenati, Fabio
last_name: Benfenati
- first_name: Katherine
full_name: Lachlan, Katherine
last_name: Lachlan
- first_name: Andreas
full_name: Benneche, Andreas
last_name: Benneche
- first_name: Florence
full_name: Petit, Florence
last_name: Petit
- first_name: Jean Madeleine
full_name: de Sainte Agathe, Jean Madeleine
last_name: de Sainte Agathe
- first_name: Barbara
full_name: Hallinan, Barbara
last_name: Hallinan
- first_name: Yue
full_name: Si, Yue
last_name: Si
- first_name: Ingrid M
full_name: Wentzensen, Ingrid M
last_name: Wentzensen
- first_name: Fanggeng
full_name: Zou, Fanggeng
last_name: Zou
- first_name: Vinodh
full_name: Narayanan, Vinodh
last_name: Narayanan
- first_name: Naomichi
full_name: Matsumoto, Naomichi
last_name: Matsumoto
- first_name: Alessandra
full_name: Boncristiano, Alessandra
last_name: Boncristiano
- first_name: Giancarlo
full_name: la Marca, Giancarlo
last_name: la Marca
- first_name: Mitsuhiro
full_name: Kato, Mitsuhiro
last_name: Kato
- first_name: Kristin
full_name: Anderson, Kristin
last_name: Anderson
- first_name: Carmen
full_name: Barba, Carmen
last_name: Barba
- first_name: Luisa
full_name: Sturiale, Luisa
last_name: Sturiale
- first_name: Domenico
full_name: Garozzo, Domenico
last_name: Garozzo
- first_name: Roberto
full_name: Bei, Roberto
last_name: Bei
- first_name: Laura
full_name: Masuelli, Laura
last_name: Masuelli
- first_name: Valerio
full_name: Conti, Valerio
last_name: Conti
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Anna
full_name: Fassio, Anna
last_name: Fassio
citation:
ama: 'Guerrini R, Mei D, Szigeti MK, et al. Phenotypic and genetic spectrum of ATP6V1A
encephalopathy: A disorder of lysosomal homeostasis. Brain. 2022;145(8):2687-2703.
doi:10.1093/brain/awac145'
apa: 'Guerrini, R., Mei, D., Szigeti, M. K., Pepe, S., Koenig, M. K., Von Allmen,
G., … Fassio, A. (2022). Phenotypic and genetic spectrum of ATP6V1A encephalopathy:
A disorder of lysosomal homeostasis. Brain. Oxford University Press. https://doi.org/10.1093/brain/awac145'
chicago: 'Guerrini, Renzo, Davide Mei, Margit Katalin Szigeti, Sara Pepe, Mary Kay
Koenig, Gretchen Von Allmen, Megan T Cho, et al. “Phenotypic and Genetic Spectrum
of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain.
Oxford University Press, 2022. https://doi.org/10.1093/brain/awac145.'
ieee: 'R. Guerrini et al., “Phenotypic and genetic spectrum of ATP6V1A encephalopathy:
A disorder of lysosomal homeostasis,” Brain, vol. 145, no. 8. Oxford University
Press, pp. 2687–2703, 2022.'
ista: 'Guerrini R, Mei D, Szigeti MK, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald
K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA,
Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB,
Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S, Maragliano L, Benfenati
F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen
IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson
K, Barba C, Sturiale L, Garozzo D, Bei R, Masuelli L, Conti V, Novarino G, Fassio
A. 2022. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder
of lysosomal homeostasis. Brain. 145(8), 2687–2703.'
mla: 'Guerrini, Renzo, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy:
A Disorder of Lysosomal Homeostasis.” Brain, vol. 145, no. 8, Oxford University
Press, 2022, pp. 2687–703, doi:10.1093/brain/awac145.'
short: R. Guerrini, D. Mei, M.K. Szigeti, S. Pepe, M.K. Koenig, G. Von Allmen, M.T.
Cho, K. McDonald, J. Baker, V. Bhambhani, Z. Powis, L. Rodan, R. Nabbout, G. Barcia,
J.A. Rosenfeld, C.A. Bacino, C. Mignot, L.H. Power, C.J. Harris, D. Marjanovic,
R.S. Møller, T.B. Hammer, R. Keski Filppula, P. Vieira, C. Hildebrandt, S. Sacharow,
L. Maragliano, F. Benfenati, K. Lachlan, A. Benneche, F. Petit, J.M. de Sainte
Agathe, B. Hallinan, Y. Si, I.M. Wentzensen, F. Zou, V. Narayanan, N. Matsumoto,
A. Boncristiano, G. la Marca, M. Kato, K. Anderson, C. Barba, L. Sturiale, D.
Garozzo, R. Bei, L. Masuelli, V. Conti, G. Novarino, A. Fassio, Brain 145 (2022)
2687–2703.
date_created: 2023-01-12T12:11:45Z
date_published: 2022-08-01T00:00:00Z
date_updated: 2023-08-04T09:13:08Z
day: '01'
department:
- _id: GaNo
doi: 10.1093/brain/awac145
ec_funded: 1
external_id:
isi:
- '000807770000001'
intvolume: ' 145'
isi: 1
issue: '8'
keyword:
- Neurology (clinical)
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1093/brain/awac145
month: '08'
oa: 1
oa_version: Published Version
page: 2687-2703
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Brain
publication_identifier:
eissn:
- 1460-2156
issn:
- 0006-8950
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal
homeostasis'
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 145
year: '2022'
...
---
_id: '12268'
abstract:
- lang: eng
text: The complexity of the microenvironment effects on cell response, show accumulating
evidence that glioblastoma (GBM) migration and invasiveness are influenced by
the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition
(EMT) is a well-recognized driving force of the invasive behavior of cancer. However,
the primary mechanisms of EMT initiation and progression remain unclear. We have
previously showed that certain substrate stiffness can selectively stimulate human
GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies
several known EMT mediators to uncover the reason of the regulation and response
to these stiffnesses. Our results revealed that changing the rigidity of the mechanical
environment tuned the response of both cell lines through change in morphological
features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions
in an interrelated manner. Specifically, a stiffer microenvironment induced a
mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic
ROS expression and lower mitochondrial ROS. Finally, we observed that cells more
motile showed a more depolarized mitochondrial membrane potential. Unravelling
the process that regulates GBM cells’ infiltrative behavior could provide new
opportunities for identification of new targets and less invasive approaches for
treatment.
acknowledgement: "The research leading to these results has received funding from
AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG
2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful
to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia:
DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia
e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE
n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for
useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela
Marchetti for practical administrative support."
article_number: '983507'
article_processing_charge: No
article_type: original
author:
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Ilaria Elena
full_name: Palamà, Ilaria Elena
last_name: Palamà
- first_name: Stefania
full_name: D’Amone, Stefania
last_name: D’Amone
- first_name: Clotilde
full_name: Lauro, Clotilde
last_name: Lauro
- first_name: Maria
full_name: Rosito, Maria
last_name: Rosito
- first_name: Maddalena
full_name: Grieco, Maddalena
last_name: Grieco
- first_name: Patrizia
full_name: Ratano, Patrizia
last_name: Ratano
- first_name: Federica
full_name: Cordella, Federica
last_name: Cordella
- first_name: Caterina
full_name: Sanchini, Caterina
last_name: Sanchini
- first_name: Silvia
full_name: Di Angelantonio, Silvia
last_name: Di Angelantonio
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
- first_name: Mariafrancesca
full_name: Cascione, Mariafrancesca
last_name: Cascione
- first_name: Giuseppe
full_name: Gigli, Giuseppe
last_name: Gigli
- first_name: Barbara
full_name: Cortese, Barbara
last_name: Cortese
citation:
ama: Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular
crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma
cells. Frontiers in Oncology. 2022;12. doi:10.3389/fonc.2022.983507
apa: Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M.,
… Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
transition mediators of human glioblastoma cells. Frontiers in Oncology.
Frontiers Media. https://doi.org/10.3389/fonc.2022.983507
chicago: Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro,
Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect
on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human
Glioblastoma Cells.” Frontiers in Oncology. Frontiers Media, 2022. https://doi.org/10.3389/fonc.2022.983507.
ieee: B. Basilico et al., “Substrate stiffness effect on molecular crosstalk
of epithelial-mesenchymal transition mediators of human glioblastoma cells,” Frontiers
in Oncology, vol. 12. Frontiers Media, 2022.
ista: Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella
F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B.
2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507.
mla: Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk
of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers
in Oncology, vol. 12, 983507, Frontiers Media, 2022, doi:10.3389/fonc.2022.983507.
short: B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P.
Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione,
G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022).
date_created: 2023-01-16T10:00:28Z
date_published: 2022-08-25T00:00:00Z
date_updated: 2023-08-04T09:54:16Z
day: '25'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3389/fonc.2022.983507
external_id:
isi:
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pmid:
- '36091138'
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content_type: application/pdf
creator: dernst
date_created: 2023-01-30T10:25:21Z
date_updated: 2023-01-30T10:25:21Z
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file_size: 13588502
relation: main_file
success: 1
file_date_updated: 2023-01-30T10:25:21Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
keyword:
- Cancer Research
- Oncology
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Oncology
publication_identifier:
issn:
- 2234-943X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
transition mediators of human glioblastoma cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2022'
...
---
_id: '10818'
abstract:
- lang: eng
text: Microglia cells are active players in regulating synaptic development and
plasticity in the brain. However, how they influence the normal functioning of
synapses is largely unknown. In this study, we characterized the effects of pharmacological
microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1
synapses of adult wild type mice. Following microglial depletion, we observed
a reduction of spontaneous and evoked glutamatergic activity associated with a
decrease of dendritic spine density. We also observed the appearance of immature
synaptic features and higher levels of plasticity. Microglia depleted mice showed
a deficit in the acquisition of the Novel Object Recognition task. These events
were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory
condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting
the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably,
microglia repopulation after PLX5622 withdrawal was associated with the recovery
of hippocampal synapses and learning functions. Altogether, these data demonstrate
that microglia contribute to normal synaptic functioning in the adult brain and
that their removal induces reversible changes in organization and activity of
glutamatergic synapses.
acknowledgement: The work was supported by a grant from MIUR (PRIN 2017HPTFFC_003)
to Davide Ragozzino and in part by funds to Silvia Di Angelantonio (CrestOptics-IIT
JointLab for Advanced Microscopy) and Daniele Caprioli (Istituto Pasteur-Fondazione
Cenci Bolognetti). Bernadette Basilico, and Laura Ferrucci were supported by the
PhD program in Clinical-Experimental Neuroscience and Psychiatry, Sapienza University,
Rome; Caterina Sanchini was supported by the PhD program in Life Science, Sapienza
University, Rome and by the Italian Institute of Technology, Rome. The authors thank
Alessandro Felici, Claudia Valeri, Arsenio Armagno, and Senthilkumar Deivasigamani
for help with animal husbandry and transgenic colonies management. They also wish
to thank Piotr Bregestovski and Michal Schwartz for helpful discussions and criticism.
PLX5622 was provided under Materials Transfer Agreement by Plexxikon Inc. (Berkeley,
CA). Open Access Funding provided by Universita degli Studi di Roma La Sapienza
within the CRUI-CARE Agreement.
article_processing_charge: No
article_type: original
author:
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Laura
full_name: Ferrucci, Laura
last_name: Ferrucci
- first_name: Patrizia
full_name: Ratano, Patrizia
last_name: Ratano
- first_name: Maria T.
full_name: Golia, Maria T.
last_name: Golia
- first_name: Alfonso
full_name: Grimaldi, Alfonso
last_name: Grimaldi
- first_name: Maria
full_name: Rosito, Maria
last_name: Rosito
- first_name: Valentina
full_name: Ferretti, Valentina
last_name: Ferretti
- first_name: Ingrid
full_name: Reverte, Ingrid
last_name: Reverte
- first_name: Caterina
full_name: Sanchini, Caterina
last_name: Sanchini
- first_name: Maria C.
full_name: Marrone, Maria C.
last_name: Marrone
- first_name: Maria
full_name: Giubettini, Maria
last_name: Giubettini
- first_name: Valeria
full_name: De Turris, Valeria
last_name: De Turris
- first_name: Debora
full_name: Salerno, Debora
last_name: Salerno
- first_name: Stefano
full_name: Garofalo, Stefano
last_name: Garofalo
- first_name: Marie‐Kim
full_name: St‐Pierre, Marie‐Kim
last_name: St‐Pierre
- first_name: Micael
full_name: Carrier, Micael
last_name: Carrier
- first_name: Massimiliano
full_name: Renzi, Massimiliano
last_name: Renzi
- first_name: Francesca
full_name: Pagani, Francesca
last_name: Pagani
- first_name: Brijesh
full_name: Modi, Brijesh
last_name: Modi
- first_name: Marcello
full_name: Raspa, Marcello
last_name: Raspa
- first_name: Ferdinando
full_name: Scavizzi, Ferdinando
last_name: Scavizzi
- first_name: Cornelius T.
full_name: Gross, Cornelius T.
last_name: Gross
- first_name: Silvia
full_name: Marinelli, Silvia
last_name: Marinelli
- first_name: Marie‐Ève
full_name: Tremblay, Marie‐Ève
last_name: Tremblay
- first_name: Daniele
full_name: Caprioli, Daniele
last_name: Caprioli
- first_name: Laura
full_name: Maggi, Laura
last_name: Maggi
- first_name: Cristina
full_name: Limatola, Cristina
last_name: Limatola
- first_name: Silvia
full_name: Di Angelantonio, Silvia
last_name: Di Angelantonio
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
citation:
ama: Basilico B, Ferrucci L, Ratano P, et al. Microglia control glutamatergic synapses
in the adult mouse hippocampus. Glia. 2022;70(1):173-195. doi:10.1002/glia.24101
apa: Basilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito,
M., … Ragozzino, D. (2022). Microglia control glutamatergic synapses in the adult
mouse hippocampus. Glia. Wiley. https://doi.org/10.1002/glia.24101
chicago: Basilico, Bernadette, Laura Ferrucci, Patrizia Ratano, Maria T. Golia,
Alfonso Grimaldi, Maria Rosito, Valentina Ferretti, et al. “Microglia Control
Glutamatergic Synapses in the Adult Mouse Hippocampus.” Glia. Wiley, 2022.
https://doi.org/10.1002/glia.24101.
ieee: B. Basilico et al., “Microglia control glutamatergic synapses in the
adult mouse hippocampus,” Glia, vol. 70, no. 1. Wiley, pp. 173–195, 2022.
ista: Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, Ferretti
V, Reverte I, Sanchini C, Marrone MC, Giubettini M, De Turris V, Salerno D, Garofalo
S, St‐Pierre M, Carrier M, Renzi M, Pagani F, Modi B, Raspa M, Scavizzi F, Gross
CT, Marinelli S, Tremblay M, Caprioli D, Maggi L, Limatola C, Di Angelantonio
S, Ragozzino D. 2022. Microglia control glutamatergic synapses in the adult mouse
hippocampus. Glia. 70(1), 173–195.
mla: Basilico, Bernadette, et al. “Microglia Control Glutamatergic Synapses in the
Adult Mouse Hippocampus.” Glia, vol. 70, no. 1, Wiley, 2022, pp. 173–95,
doi:10.1002/glia.24101.
short: B. Basilico, L. Ferrucci, P. Ratano, M.T. Golia, A. Grimaldi, M. Rosito,
V. Ferretti, I. Reverte, C. Sanchini, M.C. Marrone, M. Giubettini, V. De Turris,
D. Salerno, S. Garofalo, M. St‐Pierre, M. Carrier, M. Renzi, F. Pagani, B. Modi,
M. Raspa, F. Scavizzi, C.T. Gross, S. Marinelli, M. Tremblay, D. Caprioli, L.
Maggi, C. Limatola, S. Di Angelantonio, D. Ragozzino, Glia 70 (2022) 173–195.
date_created: 2022-03-04T08:53:37Z
date_published: 2022-01-01T00:00:00Z
date_updated: 2023-09-05T16:01:23Z
day: '01'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1002/glia.24101
external_id:
isi:
- '000708025800001'
pmid:
- '34661306'
file:
- access_level: open_access
checksum: f10a897290e66c0a062e04ba91db6c17
content_type: application/pdf
creator: dernst
date_created: 2022-03-04T08:55:27Z
date_updated: 2022-03-04T08:55:27Z
file_id: '10819'
file_name: 2021_Glia_Basilico.pdf
file_size: 5340294
relation: main_file
success: 1
file_date_updated: 2022-03-04T08:55:27Z
has_accepted_license: '1'
intvolume: ' 70'
isi: 1
issue: '1'
keyword:
- Cellular and Molecular Neuroscience
- Neurology
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '01'
oa: 1
oa_version: Published Version
page: 173-195
pmid: 1
publication: Glia
publication_identifier:
eissn:
- 1098-1136
issn:
- 0894-1491
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microglia control glutamatergic synapses in the adult mouse hippocampus
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 70
year: '2022'
...
---
_id: '11943'
abstract:
- lang: eng
text: Complex wiring between neurons underlies the information-processing network
enabling all brain functions, including cognition and memory. For understanding
how the network is structured, processes information, and changes over time, comprehensive
visualization of the architecture of living brain tissue with its cellular and
molecular components would open up major opportunities. However, electron microscopy
(EM) provides nanometre-scale resolution required for full in-silico
reconstruction1–5, yet is limited to fixed specimens and
static representations. Light microscopy allows live observation, with super-resolution
approaches6–12 facilitating nanoscale visualization, but
comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue
photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise
ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue.
We developed an integrated imaging and analysis technology, adapting stimulated
emission depletion (STED) microscopy6,13 in extracellularly
labelled tissue14 for high SNR and near-isotropic resolution.
Centrally, a two-stage deep-learning approach leveraged previously obtained information
on sample structure to drastically reduce photo-burden and enable automated volumetric
reconstruction down to single synapse level. Live reconstruction provides unbiased
analysis of tissue architecture across time in relation to functional activity
and targeted activation, and contextual understanding of molecular labelling.
This adoptable technology will facilitate novel insights into the dynamic functional
architecture of living brain tissue.
article_processing_charge: No
author:
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Eder
full_name: Miguel Villalba, Eder
id: 3FB91342-F248-11E8-B48F-1D18A9856A87
last_name: Miguel Villalba
orcid: 0000-0001-5665-0430
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Donglai
full_name: Wei, Donglai
last_name: Wei
- first_name: Zudi
full_name: Lin, Zudi
last_name: Lin
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Jakob
full_name: Troidl, Jakob
last_name: Troidl
- first_name: Johanna
full_name: Beyer, Johanna
last_name: Beyer
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Wiebke
full_name: Jahr, Wiebke
id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
last_name: Jahr
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Johannes
full_name: Broichhagen, Johannes
last_name: Broichhagen
- first_name: Seth G. N.
full_name: Grant, Seth G. N.
last_name: Grant
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Hanspeter
full_name: Pfister, Hanspeter
last_name: Pfister
- first_name: Bernd
full_name: Bickel, Bernd
id: 49876194-F248-11E8-B48F-1D18A9856A87
last_name: Bickel
orcid: 0000-0001-6511-9385
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction
of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431
apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson,
J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv.
Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431
chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei,
Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living
Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431.
ieee: P. Velicky et al., “Saturated reconstruction of living brain tissue,”
bioRxiv. Cold Spring Harbor Laboratory.
ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl
J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN,
Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction
of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431.
mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.”
BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431.
short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson,
J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen,
S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv
(n.d.).
date_created: 2022-08-23T11:07:59Z
date_published: 2022-05-09T00:00:00Z
date_updated: 2024-03-28T23:30:20Z
day: '09'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
doi: 10.1101/2022.03.16.484431
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.03.16.484431
month: '05'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Saturated reconstruction of living brain tissue
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11950'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS leverages fixation-compatible
extracellular labeling and advanced optical readout, in particular stimulated-emission
depletion and expansion microscopy, to comprehensively delineate cellular structures.
It enables 3D-reconstructing single synapses and mapping synaptic connectivity
by identification and tailored analysis of putative synaptic cleft regions. Applying
CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
the system’s molecularly informed ultrastructure across spatial scales and assess
local connectivity by reconstructing and quantifying the synaptic input and output
structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture
across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2022.08.17.504272
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272.
ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across
scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor
Laboratory.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
Uncovering brain tissue architecture across scales with super-resolution light
microscopy. bioRxiv, 10.1101/2022.08.17.504272.
mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory,
doi:10.1101/2022.08.17.504272.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
Jonas, J.G. Danzl, BioRxiv (n.d.).
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2024-03-28T23:30:20Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11160'
abstract:
- lang: eng
text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent
cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses
macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency
affects neurodevelopmental is unclear. Here, employing human cerebral organoids,
we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories
with an accelerated and delayed generation of, respectively, inhibitory and excitatory
neurons that yields, at days 60 and 120, symmetrically opposite expansions in
their proportions. This imbalance is consistent with an enlargement of cerebral
organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic
design of patient-specific mutations and mosaic organoids, we define genotype-phenotype
relationships and uncover their cell-autonomous nature. Our results define cell-type-specific
CHD8-dependent molecular defects related to an abnormal program of proliferation
and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations,
our study uncovers reproducible developmental alterations that may be employed
for neurodevelopmental disease modeling.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Farnaz Freeman for technical assistance. This research was
supported by the Scientific Service Units (SSU) of IST Austria through resources
provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This
work supported by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs);
the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele;
and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures
were created using BioRender.com.
article_number: '110615'
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlo Emanuele
full_name: Villa, Carlo Emanuele
last_name: Villa
- first_name: Cristina
full_name: Cheroni, Cristina
last_name: Cheroni
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Alejandro
full_name: López-Tóbon, Alejandro
last_name: López-Tóbon
- first_name: Bárbara
full_name: Oliveira, Bárbara
id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
last_name: Oliveira
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Aysan Çerağ
full_name: Yahya, Aysan Çerağ
id: 365A65F8-F248-11E8-B48F-1D18A9856A87
last_name: Yahya
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Michele
full_name: Gabriele, Michele
last_name: Gabriele
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Mariano
full_name: Gabitto, Mariano
last_name: Gabitto
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Giuseppe
full_name: Testa, Giuseppe
last_name: Testa
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism
to transient alterations in excitatory and inhibitory trajectories. Cell Reports.
2022;39(1). doi:10.1016/j.celrep.2022.110615
apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco,
R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615
chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon,
Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency
Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.”
Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615.
ieee: C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient
alterations in excitatory and inhibitory trajectories,” Cell Reports, vol.
39, no. 1. Elsevier, 2022.
ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ,
Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG,
Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.
mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient
Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol.
39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.
short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco,
A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer,
M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2024-03-28T23:30:45Z
day: '05'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
ec_funded: 1
external_id:
isi:
- '000785983900003'
pmid:
- '35385734'
file:
- access_level: open_access
checksum: b4e8d68f0268dec499af333e6fd5d8e1
content_type: application/pdf
creator: dernst
date_created: 2022-04-15T09:06:25Z
date_updated: 2022-04-15T09:06:25Z
file_id: '11164'
file_name: 2022_CellReports_Villa.pdf
file_size: '7808644'
relation: main_file
success: 1
file_date_updated: 2022-04-15T09:06:25Z
has_accepted_license: '1'
intvolume: ' 39'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I04205
name: Identification of converging Molecular Pathways Across Chromatinopathies as
Targets for Therapy
publication: Cell Reports
publication_identifier:
issn:
- 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12364'
relation: dissertation_contains
status: public
status: public
title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
and inhibitory trajectories
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 39
year: '2022'
...
---
_id: '12364'
abstract:
- lang: eng
text: "Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders
character\x02ized by behavioral symptoms such as problems in social communication
and interaction, as\r\nwell as repetitive, restricted behaviors and interests.
These disorders show a high degree\r\nof heritability and hundreds of risk genes
have been identifed using high throughput\r\nsequencing technologies. This genetic
heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD
but at the same time given rise to the concept of convergent\r\nmechanisms. Previous
studies have identifed that risk genes for ASD broadly converge\r\nonto specifc
functional categories with transcriptional regulation being one of the biggest\r\ngroups.
In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences
of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations
in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations
of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult
animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel
by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe
link the regulatory function of Setd5 to its interaction with the Paf1 and the
NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene
CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental
trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing.
While the former\r\nwere generated earlier in CHD8+/- organoids, the generation
of the latter was shifted to\r\nlater times in favor of a prolonged progenitor
expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling
heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B,
KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory
convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory
neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral
ganglionic eminence. As this project is still ongoing at the time of writing,
future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying
this shift with\r\nthe aim of linking these three ASD risk genes through biological
convergence."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
citation:
ama: Dotter C. Transcriptional consequences of mutations in genes associated with
Autism Spectrum Disorder. 2022. doi:10.15479/at:ista:12094
apa: Dotter, C. (2022). Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria.
https://doi.org/10.15479/at:ista:12094
chicago: Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes
Associated with Autism Spectrum Disorder.” Institute of Science and Technology
Austria, 2022. https://doi.org/10.15479/at:ista:12094.
ieee: C. Dotter, “Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022.
ista: Dotter C. 2022. Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria.
mla: Dotter, Christoph. Transcriptional Consequences of Mutations in Genes Associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria,
2022, doi:10.15479/at:ista:12094.
short: C. Dotter, Transcriptional Consequences of Mutations in Genes Associated
with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.
date_created: 2023-01-24T13:09:57Z
date_published: 2022-09-19T00:00:00Z
date_updated: 2023-11-16T13:10:22Z
day: '19'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaNo
doi: 10.15479/at:ista:12094
ec_funded: 1
file:
- access_level: open_access
checksum: 896f4cac9adb6d3f26a6605772f4e1a3
content_type: application/pdf
creator: cchlebak
date_created: 2023-01-24T13:15:45Z
date_updated: 2023-09-20T22:30:03Z
embargo: 2023-09-19
file_id: '12365'
file_name: 220923_Thesis_CDotter_Final.pdf
file_size: 20457465
relation: main_file
- access_level: closed
checksum: ad01bb20da163be6893b7af832e58419
content_type: application/x-zip-compressed
creator: cchlebak
date_created: 2023-02-02T09:15:35Z
date_updated: 2023-09-20T22:30:03Z
embargo_to: open_access
file_id: '12482'
file_name: latex_source_CDotter_Thesis_2022.zip
file_size: 22433512
relation: source_file
file_date_updated: 2023-09-20T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '152'
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
grant_number: '401299'
name: Probing development and reversibility of autism spectrum disorders
- _id: 9B91375C-BA93-11EA-9121-9846C619BF3A
grant_number: '707964'
name: Critical windows and reversibility of ASD associated with mutations in chromatin
remodelers
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I04205
name: Identification of converging Molecular Pathways Across Chromatinopathies as
Targets for Therapy
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '3'
relation: part_of_dissertation
status: public
- id: '11160'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: Transcriptional consequences of mutations in genes associated with Autism Spectrum
Disorder
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '10281'
abstract:
- lang: eng
text: Mutations affecting mTOR or RAS signaling underlie defined syndromes (the
so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder
(ASD). These syndromes show a broad variety of somatic phenotypes including cancers,
skin abnormalities, heart disease and facial dysmorphisms. Less well studied are
the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these
signalopathies in ASD reviewing genetic, human cell model, rodent studies and
clinical trials. We conclude that signalopathies have an increased liability for
ASD and that, in particular, ASD individuals with dysmorphic features and intellectual
disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related
genes. Studies on rodent and human cell models confirm aberrant neuronal development
as the underlying pathology. Human studies further suggest that multiple hits
are necessary to induce the respective phenotypes. Recent clinical trials do only
report improvements for comorbid conditions such as epilepsy or cancer but not
for behavioral aspects. Animal models show that treatment during early development
can rescue behavioral phenotypes. Taken together, we suggest investigating the
differential roles of mTOR and RAS signaling in both human and rodent models,
and to test drug treatment both during and after neuronal development in the available
model systems
acknowledgement: 'This review was funded by the IMI2 Initiative under the grant AIMS-2-TRIALS
No 777394, by the Hessian Ministry for Science and Arts; State of Hesse Ministry
for Science and Arts: LOEWE-Grant to the CePTER-Consortium (www.uni-frankfurt.de/67689811);
Research (BMBF) under the grant RAISE-genic No 779282 all to AGC. This work was
also supported by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 715508 (REVERSEAUTISM) and by the Austrian Science Fund (FWF) (DK W1232-B24)
both to G.N. and both BMBF GeNeRARe 01GM1519A and CRC 1080, project B10, of the
German Research Foundation (DFG) to M.J.S, respectively. We want to thank R. Waltes
for her support in preparing this manuscript.'
alternative_title:
- Special Issue "From Genes to Therapy in Autism Spectrum Disorder"
article_number: '1746'
article_processing_charge: No
article_type: original
author:
- first_name: Verica
full_name: Vasic, Verica
last_name: Vasic
- first_name: Mattson S.O.
full_name: Jones, Mattson S.O.
last_name: Jones
- first_name: Denise
full_name: Haslinger, Denise
id: 76922BDA-3D3B-11EA-90BD-A44F3DDC885E
last_name: Haslinger
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Michael J.
full_name: Schmeisser, Michael J.
last_name: Schmeisser
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Andreas G.
full_name: Chiocchetti, Andreas G.
last_name: Chiocchetti
citation:
ama: 'Vasic V, Jones MSO, Haslinger D, et al. Translating the role of mtor-and ras-associated
signalopathies in autism spectrum disorder: Models, mechanisms and treatment.
Genes. 2021;12(11). doi:10.3390/genes12111746'
apa: 'Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino,
G., & Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated
signalopathies in autism spectrum disorder: Models, mechanisms and treatment.
Genes. MDPI. https://doi.org/10.3390/genes12111746'
chicago: 'Vasic, Verica, Mattson S.O. Jones, Denise Haslinger, Lisa Knaus, Michael
J. Schmeisser, Gaia Novarino, and Andreas G. Chiocchetti. “Translating the Role
of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models,
Mechanisms and Treatment.” Genes. MDPI, 2021. https://doi.org/10.3390/genes12111746.'
ieee: 'V. Vasic et al., “Translating the role of mtor-and ras-associated
signalopathies in autism spectrum disorder: Models, mechanisms and treatment,”
Genes, vol. 12, no. 11. MDPI, 2021.'
ista: 'Vasic V, Jones MSO, Haslinger D, Knaus L, Schmeisser MJ, Novarino G, Chiocchetti
AG. 2021. Translating the role of mtor-and ras-associated signalopathies in autism
spectrum disorder: Models, mechanisms and treatment. Genes. 12(11), 1746.'
mla: 'Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies
in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” Genes,
vol. 12, no. 11, 1746, MDPI, 2021, doi:10.3390/genes12111746.'
short: V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino,
A.G. Chiocchetti, Genes 12 (2021).
date_created: 2021-11-14T23:01:24Z
date_published: 2021-10-30T00:00:00Z
date_updated: 2023-08-14T11:46:12Z
day: '30'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3390/genes12111746
ec_funded: 1
external_id:
isi:
- '000834044200002'
file:
- access_level: open_access
checksum: 256cb832a9c3051c7dc741f6423b8cbd
content_type: application/pdf
creator: dernst
date_created: 2022-05-16T07:02:27Z
date_updated: 2022-05-16T07:02:27Z
file_id: '11380'
file_name: 2021_Genes_Vasic.pdf
file_size: 1335308
relation: main_file
success: 1
file_date_updated: 2022-05-16T07:02:27Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '11'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: Genes
publication_identifier:
eissn:
- 2073-4425
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Translating the role of mtor-and ras-associated signalopathies in autism spectrum
disorder: Models, mechanisms and treatment'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '10301'
abstract:
- lang: eng
text: De novo protein synthesis is required for synapse modifications underlying
stable memory encoding. Yet neurons are highly compartmentalized cells and how
protein synthesis can be regulated at the synapse level is unknown. Here, we characterize
neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic
target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to
mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A
subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR
complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR
activation and restricts the mTOR-dependent translation of specific activity-regulated
mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent
protein synthesis, and facilitates the consolidation of associative and spatial
memories in mice. The memory enhancement becomes evident with light or spaced
training, can be achieved by selectively deleting GluN3A from excitatory neurons
during adulthood, and does not compromise other aspects of cognition such as memory
flexibility or extinction. Our findings provide mechanistic insight into synaptic
translational control and reveal a potentially selective target for cognitive
enhancement.
acknowledgement: We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a
knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral
and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and
Ana Navarro for expert technical help. Work was funded by the UTE project CIMA;
fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO
(to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.),
FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.);
ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program
RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077
FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637)
and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator
Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R),
Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence
Awards (SEV-2013-0317, SEV-2017-0723).
article_number: e71575
article_processing_charge: No
article_type: original
author:
- first_name: María J
full_name: Conde-Dusman, María J
last_name: Conde-Dusman
- first_name: Partha N
full_name: Dey, Partha N
last_name: Dey
- first_name: Óscar
full_name: Elía-Zudaire, Óscar
last_name: Elía-Zudaire
- first_name: Luis E
full_name: Garcia Rabaneda, Luis E
id: 33D1B084-F248-11E8-B48F-1D18A9856A87
last_name: Garcia Rabaneda
- first_name: Carmen
full_name: García-Lira, Carmen
last_name: García-Lira
- first_name: Teddy
full_name: Grand, Teddy
last_name: Grand
- first_name: Victor
full_name: Briz, Victor
last_name: Briz
- first_name: Eric R
full_name: Velasco, Eric R
last_name: Velasco
- first_name: Raül
full_name: Andero Galí, Raül
last_name: Andero Galí
- first_name: Sergio
full_name: Niñerola, Sergio
last_name: Niñerola
- first_name: Angel
full_name: Barco, Angel
last_name: Barco
- first_name: Pierre
full_name: Paoletti, Pierre
last_name: Paoletti
- first_name: John F
full_name: Wesseling, John F
last_name: Wesseling
- first_name: Fabrizio
full_name: Gardoni, Fabrizio
last_name: Gardoni
- first_name: Steven J
full_name: Tavalin, Steven J
last_name: Tavalin
- first_name: Isabel
full_name: Perez-Otaño, Isabel
last_name: Perez-Otaño
citation:
ama: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis
and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
eLife. 2021;10. doi:10.7554/elife.71575
apa: Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E.,
García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis
and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575
chicago: Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia
Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein
Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1
Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.
ieee: M. J. Conde-Dusman et al., “Control of protein synthesis and memory
by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife,
vol. 10. eLife Sciences Publications, 2021.
ista: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C,
Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling
JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and
memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife.
10, e71575.
mla: Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by
GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife,
vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575.
short: M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira,
T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti,
J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).
date_created: 2021-11-18T06:59:45Z
date_published: 2021-11-17T00:00:00Z
date_updated: 2023-08-14T11:50:50Z
day: '17'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.7554/elife.71575
external_id:
isi:
- '000720945900001'
file:
- access_level: open_access
checksum: 59318e9e41507cec83c2f4070e6ad540
content_type: application/pdf
creator: lgarciar
date_created: 2021-11-18T07:02:02Z
date_updated: 2021-11-18T07:02:02Z
file_id: '10302'
file_name: elife-71575-v1.pdf
file_size: 2477302
relation: main_file
success: 1
file_date_updated: 2021-11-18T07:02:02Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
keyword:
- general immunology and microbiology
- general biochemistry
- genetics and molecular biology
- general medicine
- general neuroscience
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
status: public
title: Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition
of GIT1/mTORC1 assembly
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_id: '9953'
abstract:
- lang: eng
text: Chronic psychological stress is one of the most important triggers and environmental
risk factors for neuropsychiatric disorders. Chronic stress can influence all
organs via the secretion of stress hormones, including glucocorticoids by the
adrenal glands, which coordinate the stress response across the body. In the brain,
glucocorticoid receptors (GR) are expressed by various cell types including microglia,
which are its resident immune cells regulating stress-induced inflammatory processes.
To study the roles of microglial GR under normal homeostatic conditions and following
chronic stress, we generated a mouse model in which the GR gene is depleted in
microglia specifically at adulthood to prevent developmental confounds. We first
confirmed that microglia were depleted in GR in our model in males and females
among the cingulate cortex and the hippocampus, both stress-sensitive brain regions.
Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were
housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable
mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR
depleted and WT animals as demonstrated by a decrease of both saccharine preference
and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and
neural mechanisms underlying the adaptation to stress occurred differently between
the two genotypes. Upon CUMS exposure, microglial morphology was altered in the
WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore,
in the standard environment condition, GR depleted-microglia showed increased
expression of pro-inflammatory genes, and genes involved in microglial homeostatic
functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition,
GR depleted-microglia showed reduced expression levels of pro-inflammatory genes
and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia.
Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant
reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences
in adult hippocampal neurogenesis were observed between the genotypes during normal
homeostatic conditions, with microglial-GR deficiency increasing the formation
of newborn neurons in the dentate gyrus subgranular zone independently from stress
exposure. Together, these findings indicate that, although the deletion of microglial
GR did not prevent the animal’s ability to respond to stress, it contributed to
modulating hippocampal functions in both standard and stressful conditions, notably
by shaping the microglial response to chronic stress.
acknowledgement: We acknowledge that Université Laval stands on the traditional and
unceded land of the Huron-Wendat peoples; and that the University of Victoria exists
on the territory of the Lekwungen peoples and that the Songhees, Esquimalt and WSÁNEÆ
peoples have relationships to this land. We thank Emmanuel Planel for the access
to the epifluorescence microscope and Julie-Christine Lévesque at the Bioimaging
Platform of CRCHU de Québec-Université Laval for technical assistance. We also thank
the Centre for Advanced Materials and Related Technology for the access to the confocal
microscope with Airyscan. K.P. was supported by a doctoral scholarship from Fonds
de Recherche du Québec – Santé (FRQS), an excellence award from Fondation du CHU
de Québec, as well as from Centre Thématique de Recherche en Neurosciences and from
Fondation Famille-Choquette. K.B. was supported by excellence scholarships from
Université Laval and Fondation du CHU de Québec. S.G. is supported by FIRC-AIRC
fellowship for Italy 22329/2018 and by Pilot ARISLA NKINALS 2019. C.W.H. and J.C.S.
were supported by postdoctoral fellowships from FRQS. This study was funded by a
Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant
(RGPIN-2014-05308) awarded to M.E.T., by ERANET neuron 2017 MicroSynDep to M.E.T.
and I.B., and by the Italian Ministry of Health, grant RF-2018-12367249 to I.B,
by PRIN 2017, AIRC 2019 and Ministero della Salute RF2018 to C.L. M.E.T. is a Tier
II Canada Research Chair in Neurobiology of Aging and Cognition.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine
full_name: Picard, Katherine
last_name: Picard
- first_name: Kanchan
full_name: Bisht, Kanchan
last_name: Bisht
- first_name: Silvia
full_name: Poggini, Silvia
last_name: Poggini
- first_name: Stefano
full_name: Garofalo, Stefano
last_name: Garofalo
- first_name: Maria Teresa
full_name: Golia, Maria Teresa
last_name: Golia
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Fatima
full_name: Abdallah, Fatima
last_name: Abdallah
- first_name: Naomi
full_name: Ciano Albanese, Naomi
last_name: Ciano Albanese
- first_name: Irmgard
full_name: Amrein, Irmgard
last_name: Amrein
- first_name: Nathalie
full_name: Vernoux, Nathalie
last_name: Vernoux
- first_name: Kaushik
full_name: Sharma, Kaushik
last_name: Sharma
- first_name: Chin Wai
full_name: Hui, Chin Wai
last_name: Hui
- first_name: Julie
full_name: C. Savage, Julie
last_name: C. Savage
- first_name: Cristina
full_name: Limatola, Cristina
last_name: Limatola
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
- first_name: Laura
full_name: Maggi, Laura
last_name: Maggi
- first_name: Igor
full_name: Branchi, Igor
last_name: Branchi
- first_name: Marie Ève
full_name: Tremblay, Marie Ève
last_name: Tremblay
citation:
ama: Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion
alters the response of hippocampal microglia and neurons in a chronic unpredictable
mild stress paradigm in female mice. Brain, Behavior, and Immunity. 2021;97:423-439.
doi:10.1016/j.bbi.2021.07.022
apa: Picard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B.,
… Tremblay, M. È. (2021). Microglial-glucocorticoid receptor depletion alters
the response of hippocampal microglia and neurons in a chronic unpredictable mild
stress paradigm in female mice. Brain, Behavior, and Immunity. Elsevier.
https://doi.org/10.1016/j.bbi.2021.07.022
chicago: Picard, Katherine, Kanchan Bisht, Silvia Poggini, Stefano Garofalo, Maria
Teresa Golia, Bernadette Basilico, Fatima Abdallah, et al. “Microglial-Glucocorticoid
Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in
a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior,
and Immunity. Elsevier, 2021. https://doi.org/10.1016/j.bbi.2021.07.022.
ieee: K. Picard et al., “Microglial-glucocorticoid receptor depletion alters
the response of hippocampal microglia and neurons in a chronic unpredictable mild
stress paradigm in female mice,” Brain, Behavior, and Immunity, vol. 97.
Elsevier, pp. 423–439, 2021.
ista: Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, Abdallah F,
Ciano Albanese N, Amrein I, Vernoux N, Sharma K, Hui CW, C. Savage J, Limatola
C, Ragozzino D, Maggi L, Branchi I, Tremblay MÈ. 2021. Microglial-glucocorticoid
receptor depletion alters the response of hippocampal microglia and neurons in
a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior,
and Immunity. 97, 423–439.
mla: Picard, Katherine, et al. “Microglial-Glucocorticoid Receptor Depletion Alters
the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild
Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity, vol. 97,
Elsevier, 2021, pp. 423–39, doi:10.1016/j.bbi.2021.07.022.
short: K. Picard, K. Bisht, S. Poggini, S. Garofalo, M.T. Golia, B. Basilico, F.
Abdallah, N. Ciano Albanese, I. Amrein, N. Vernoux, K. Sharma, C.W. Hui, J. C.
Savage, C. Limatola, D. Ragozzino, L. Maggi, I. Branchi, M.È. Tremblay, Brain,
Behavior, and Immunity 97 (2021) 423–439.
date_created: 2021-08-22T22:01:21Z
date_published: 2021-10-01T00:00:00Z
date_updated: 2023-10-03T09:49:18Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.bbi.2021.07.022
external_id:
isi:
- '000702878400007'
pmid:
- '34343616'
intvolume: ' 97'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf
month: '10'
oa: 1
oa_version: Submitted Version
page: 423-439
pmid: 1
publication: Brain, Behavior, and Immunity
publication_identifier:
issn:
- 0889-1591
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microglial-glucocorticoid receptor depletion alters the response of hippocampal
microglia and neurons in a chronic unpredictable mild stress paradigm in female
mice
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 97
year: '2021'
...
---
_id: '8730'
abstract:
- lang: eng
text: P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict
at the blood–brain barrier (BBB) the brain distribution of the majority of currently
known molecularly targeted anticancer drugs. To improve brain delivery of dual
ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously
at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition
with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution
of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques
with PET. Tolerability of the erlotinib/tariquidar combination was assessed in
human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline
brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3).
Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold
and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar
alone led to less pronounced VT,brain increases in both species. Treatment of
cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent
apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete
ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted
EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly
targeted anticancer drugs for a more effective treatment of brain tumors.
article_processing_charge: No
article_type: original
author:
- first_name: N
full_name: Tournier, N
last_name: Tournier
- first_name: S
full_name: Goutal, S
last_name: Goutal
- first_name: S
full_name: Mairinger, S
last_name: Mairinger
- first_name: IH
full_name: Lozano, IH
last_name: Lozano
- first_name: T
full_name: Filip, T
last_name: Filip
- first_name: M
full_name: Sauberer, M
last_name: Sauberer
- first_name: F
full_name: Caillé, F
last_name: Caillé
- first_name: L
full_name: Breuil, L
last_name: Breuil
- first_name: J
full_name: Stanek, J
last_name: Stanek
- first_name: AF
full_name: Freeman, AF
last_name: Freeman
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: C
full_name: Truillet, C
last_name: Truillet
- first_name: T
full_name: Wanek, T
last_name: Wanek
- first_name: O
full_name: Langer, O
last_name: Langer
citation:
ama: Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and
ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to
improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal
of Cerebral Blood Flow and Metabolism. 2021;41(7):1634-1646. doi:10.1177/0271678X20965500
apa: Tournier, N., Goutal, S., Mairinger, S., Lozano, I., Filip, T., Sauberer, M.,
… Langer, O. (2021). Complete inhibition of ABCB1 and ABCG2 at the blood-brain
barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of
the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow
and Metabolism. SAGE Publications. https://doi.org/10.1177/0271678X20965500
chicago: Tournier, N, S Goutal, S Mairinger, IH Lozano, T Filip, M Sauberer, F Caillé,
et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion
of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2
Substrate [11C]Erlotinib.” Journal of Cerebral Blood Flow and Metabolism.
SAGE Publications, 2021. https://doi.org/10.1177/0271678X20965500.
ieee: N. Tournier et al., “Complete inhibition of ABCB1 and ABCG2 at the
blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain
delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” Journal of Cerebral
Blood Flow and Metabolism, vol. 41, no. 7. SAGE Publications, pp. 1634–1646,
2021.
ista: Tournier N, Goutal S, Mairinger S, Lozano I, Filip T, Sauberer M, Caillé F,
Breuil L, Stanek J, Freeman A, Novarino G, Truillet C, Wanek T, Langer O. 2021.
Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion
of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2
substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 41(7),
1634–1646.
mla: Tournier, N., et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain
Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of
the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Journal of Cerebral Blood
Flow and Metabolism, vol. 41, no. 7, SAGE Publications, 2021, pp. 1634–46,
doi:10.1177/0271678X20965500.
short: N. Tournier, S. Goutal, S. Mairinger, I. Lozano, T. Filip, M. Sauberer, F.
Caillé, L. Breuil, J. Stanek, A. Freeman, G. Novarino, C. Truillet, T. Wanek,
O. Langer, Journal of Cerebral Blood Flow and Metabolism 41 (2021) 1634–1646.
date_created: 2020-11-06T08:39:01Z
date_published: 2021-07-01T00:00:00Z
date_updated: 2023-10-18T06:45:30Z
day: '01'
department:
- _id: GaNo
doi: 10.1177/0271678X20965500
external_id:
isi:
- '000664214100012'
pmid:
- '33081568'
intvolume: ' 41'
isi: 1
issue: '7'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/
month: '07'
oa: 1
oa_version: Published Version
page: 1634-1646
pmid: 1
publication: Journal of Cerebral Blood Flow and Metabolism
publication_identifier:
eissn:
- 1559-7016
issn:
- 0271-678x
publication_status: published
publisher: SAGE Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion
of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate
[11C]erlotinib
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 41
year: '2021'
...