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dc.contributor.authorLombardo,Michael V.en
dc.contributor.authorMoon, H. M.en
dc.contributor.authorSu, J.en
dc.contributor.authorPalmer, T. D.en
dc.contributor.authorCourchesne, Ericen
dc.contributor.authorPramparo, Tizianoen
dc.creatorLombardo,Michael V.en
dc.creatorMoon, H. M.en
dc.creatorSu, J.en
dc.creatorPalmer, T. D.en
dc.creatorCourchesne, Ericen
dc.creatorPramparo, Tizianoen
dc.date.accessioned2017-07-27T10:22:00Z
dc.date.available2017-07-27T10:22:00Z
dc.date.issued2017
dc.identifier.urihttps://gnosis.library.ucy.ac.cy/handle/7/37458
dc.description.abstractMaternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates rat fetal brain gene expression (at a time point analogous to the end of the first trimester of human gestation) in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD-associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations. MIA also downregulates expression of many genes also known to be persistently downregulated in the ASD cortex later in life and which are canonically known for roles in affecting prenatally late developmental processes at the synapse. Transcriptional and translational programs that are downstream targets of highly ASD-penetrant FMR1 and CHD8 genes are also heavily affected by MIA. MIA strongly upregulates expression of a large number of genes involved in translation initiation, cell cycle, DNA damage and proteolysis processes that affect multiple key neural developmental functions. Upregulation of translation initiation is common to and preserved in gene network structure with the ASD cortical transcriptome throughout life and has downstream impact on cell cycle processes. The cap-dependent translation initiation gene, EIF4E, is one of the most MIA-dysregulated of all ASD-associated genes and targeted network analyses demonstrate prominent MIA-induced transcriptional dysregulation of mTOR and EIF4E-dependent signaling. This dysregulation of translation initiation via alteration of the Tsc2–mTor–Eif4e axis was further validated across MIA rodent models. MIA may confer increased risk for ASD by dysregulating key aspects of fetal brain gene expression that are highly relevant to pathophysiology affecting ASD.Molecular Psychiatry advance online publication, 21 March 2017; doi:10.1038/mp.2017.15. © 2017 The Author(s)en
dc.sourceMolecular psychiatryen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85015688734&doi=10.1038%2fmp.2017.15&partnerID=40&md5=5eb097c3a13d816a01f7290dfbd7930c
dc.titleMaternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorderen
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/mp.2017.15
dc.author.facultyΣχολή Κοινωνικών Επιστημών και Επιστημών Αγωγής / Faculty of Social Sciences and Education
dc.author.departmentΤμήμα Ψυχολογίας / Department of Psychology
dc.type.uhtypeArticleen
dc.description.notesCited By :1; Export Date: 17 July 2017; Article in Pressen
dc.source.abbreviationMol.Psychiatryen
dc.contributor.orcidLombardo, Michael V. [0000-0001-6780-8619]


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