---
_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'
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'
...