---
_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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checksum: 4b69a4ac0bbf4163d59c0b58dcb4f2c3
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: lknaus
date_created: 2023-06-01T13:48:41Z
date_updated: 2023-06-01T13:48:41Z
file_id: '13112'
file_name: Thesis_Lisa Knaus_approved_final.docx
file_size: 12991551
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checksum: 6903d152aa01181d87a696085af31c83
content_type: application/pdf
creator: lknaus
date_created: 2023-06-02T09:47:29Z
date_updated: 2023-06-07T08:41:49Z
file_id: '13114'
file_name: Thesis_Lisa Knaus_approved_final_pdfa2b.pdf
file_size: 9309015
relation: main_file
file_date_updated: 2023-06-07T08:41:49Z
has_accepted_license: '1'
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:
- '000856524900001'
pmid:
- '36091138'
file:
- access_level: open_access
checksum: efc7edf9f626af31853790c5b598a68c
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T10:25:21Z
date_updated: 2023-01-30T10:25:21Z
file_id: '12450'
file_name: 2022_FrontiersOntology_Basilico.pdf
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
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: 2024-03-27T23:30:20Z
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: 2024-03-27T23:30:20Z
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: 2024-03-27T23:30:44Z
day: '05'
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department:
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- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
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title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
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