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dc.contributor.author
Zerbi, Valerio
dc.contributor.author
Markicevic, Marija
dc.contributor.author
Gasparini, Fabrizio
dc.contributor.author
Schroeter, Aileen
dc.contributor.author
Rudin, Markus
dc.contributor.author
Wenderoth, Nicole
dc.date.accessioned
2019-03-12T09:20:13Z
dc.date.available
2019-03-08T20:19:26Z
dc.date.available
2019-03-12T09:20:13Z
dc.date.issued
2019-05-01
dc.identifier.issn
1053-8119
dc.identifier.issn
1095-9572
dc.identifier.other
10.1016/j.neuroimage.2019.02.051
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/330219
dc.identifier.doi
10.3929/ethz-b-000330219
dc.description.abstract
Previous work has demonstrated that neuroimaging biomarkers which capture functional connectivity of the brain can be used to define a specific and robust endophenotype in Fmr1-/y mice, a well-established animal model of human Fragile-X Syndrome (FXS). However, it is currently unknown whether this macroscopic measure of brain connectivity is sufficiently sensitive to reliably detect changes caused by pharmacological interventions. Here we inhibited the activity of the metabotropic glutamate receptor-5 (mGluR5) using AFQ056/Mavoglurant, a drug that is assumed to normalize excitatory/inhibitory neural signaling imbalances in FXS. We employed resting-state-fMRI (rs-fMRI) and diffusion-weighted imaging (DWI) to test whether Mavoglurant re-established brain connectivity - at least partly - within some of the affected circuits in Fmr1-/y mice that are related to social behavior deficits. In line with previous findings, we observed that Fmr1-/y mice exhibited impaired social interaction, reduced connectivity in three main functional networks and altered network topology. At the group level, Mavoglurant did neither rescue abnormal social behavioral nor white matter abnormalities; however, for some, but not all of these circuits Mavoglurant had a genotype-specific effect of restoring functional connectivity. These results show that rs-fMRI connectivity is sufficiently sensitive to pick up system-level changes after the pharmacological inhibition of mGluR5 activity. However, our results also show that the effects of Mavoglurant are confined to specific networks suggesting that behavioral benefits might be restricted to narrow functional domains.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Fragile-X
en_US
dc.subject
FMR1
en_US
dc.subject
Autism
en_US
dc.subject
Brain connectivity
en_US
dc.subject
resting-state functional MRI
en_US
dc.subject
mGluR5
en_US
dc.title
Inhibiting mGluR5 activity by AFQ056/Mavoglurant rescues circuit-specific functional connectivity in Fmr1 knockout mice
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2019-02-23
ethz.journal.title
NeuroImage
ethz.journal.volume
191
en_US
ethz.journal.abbreviated
NeuroImage
ethz.pages.start
392
en_US
ethz.pages.end
402
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Pharmacogenetic fMRI in brain circuits underlying social motivation and repetitive behavior
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Amsterdam
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02535 - Institut für Bewegungswiss. und Sport / Institut of Human Movement Sc. and Sport::03963 - Wenderoth, Nicole / Wenderoth, Nicole
en_US
ethz.grant.agreementno
173984
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
ethz.relation.isSupplementedBy
10.3929/ethz-b-000327762
ethz.date.deposited
2019-03-08T20:19:27Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-03-12T09:20:59Z
ethz.rosetta.lastUpdated
2019-03-12T09:20:59Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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