Show simple item record

dc.contributor.authorConnor, Caroline M.
dc.contributor.authorDincer, Aslihan
dc.contributor.authorStraubhaar, Juerg R.
dc.contributor.authorGaller, Janina R.
dc.contributor.authorHouston, Isaac B.
dc.contributor.authorAkbarian, Schahram
dc.date2022-08-11T08:08:54.000
dc.date.accessioned2022-08-23T16:11:46Z
dc.date.available2022-08-23T16:11:46Z
dc.date.issued2012-07-15
dc.date.submitted2012-07-18
dc.identifier.citation<p>Schizophr Res. 2012 Sep;140(1-3):175-84. Epub 2012 Jul 16., doi:10.1016/j.schres.2012.06.037. <a href="http://dx.doi.org/10.1016/j.schres.2012.06.037" target="_blank">Link to article on publisher's site</a></p>
dc.identifier.doi10.1016/j.schres.2012.06.037
dc.identifier.pmid22804924
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33247
dc.description<p>Co-author Caroline Connor is a student in the Neuroscience and MD/PhD programs in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School. Aslihan Dincer is a student in GSBS' Bioinformatics and Computational Biology program.</p>
dc.description.abstractMaternal immune activation during prenatal development, including treatment with the viral RNA mimic, polyriboinosinic–polyribocytidilic acid (poly IC), serves as a widely used animal model to induce behavioral deficits reminiscent of schizophrenia and related disease. Here, we report that massive cytokine activation after a single dose of poly IC in the prenatal period is associated with lasting working memory deficits in adult offspring. To explore whether dysregulated gene expression in cerebral cortex, contributes to cognitive dysfunction, we profiled the cortical transcriptome, and in addition, mapped the genome-wide distribution of trimethylated histone H3-lysine 4 (H3K4me3), an epigenetic mark sharply regulated at the 5′ end of transcriptional units. However, deep sequencing-based H3K4me3 mapping and mRNA profiling by microarray did not reveal significant alterations in mature cerebral cortex after poly IC exposure at embryonic days E17.5 or E12.5. At a small set of genes (including suppressor of cytokine signaling Socs3), H3K4me3 was sensitive to activation of cytokine signaling in primary cultures from fetal forebrain but adult cortex of saline- and poly IC-exposed mice did not show significant differences. A limited set of transcription start sites (TSS), including Disrupted-in-Schizophrenia 1 (Disc1), a schizophrenia risk gene often implicated in gene–environment interaction models, showed altered H3K4me3 after prenatal poly IC but none of these differences survived after correcting for multiple comparisons. We conclude that prenatal poly IC is associated with cognitive deficits later in life, but without robust alterations in epigenetic regulation of gene expression in the cerebral cortex.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=22804924&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.schres.2012.06.037
dc.subjectImmunity; Adjuvants, Immunologic; Poly I-C; Psychotic Disorders; Transcriptome; Epigenesis, Genetic; Cerebral Cortex
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectNeuroscience and Neurobiology
dc.subjectPsychiatry
dc.titleMaternal immune activation alters behavior in adult offspring, with subtle changes in the cortical transcriptome and epigenome
dc.typeJournal Article
dc.source.journaltitleSchizophrenia Research
dc.source.volume140
dc.source.issue1-3
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2791&amp;context=gsbs_sp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1781
dc.identifier.contextkey3112175
refterms.dateFOA2022-08-23T16:11:46Z
html.description.abstract<p>Maternal immune activation during prenatal development, including treatment with the viral RNA mimic, polyriboinosinic–polyribocytidilic acid (poly IC), serves as a widely used animal model to induce behavioral deficits reminiscent of schizophrenia and related disease. Here, we report that massive cytokine activation after a single dose of poly IC in the prenatal period is associated with lasting working memory deficits in adult offspring. To explore whether dysregulated gene expression in cerebral cortex, contributes to cognitive dysfunction, we profiled the cortical transcriptome, and in addition, mapped the genome-wide distribution of trimethylated histone H3-lysine 4 (H3K4me3), an epigenetic mark sharply regulated at the 5′ end of transcriptional units. However, deep sequencing-based H3K4me3 mapping and mRNA profiling by microarray did not reveal significant alterations in mature cerebral cortex after poly IC exposure at embryonic days E17.5 or E12.5. At a small set of genes (including suppressor of cytokine signaling <em>Socs3</em>), H3K4me3 was sensitive to activation of cytokine signaling in primary cultures from fetal forebrain but adult cortex of saline- and poly IC-exposed mice did not show significant differences. A limited set of transcription start sites (TSS), including <em>Disrupted-in-Schizophrenia 1</em> (<em>Disc1</em>), a schizophrenia risk gene often implicated in gene–environment interaction models, showed altered H3K4me3 after prenatal poly IC but none of these differences survived after correcting for multiple comparisons. We conclude that prenatal poly IC is associated with cognitive deficits later in life, but without robust alterations in epigenetic regulation of gene expression in the cerebral cortex.</p>
dc.identifier.submissionpathgsbs_sp/1781
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Psychiatry, Brudnick Neuropsychiatric Research Institute
dc.source.pages175-84
dc.contributor.studentAslihan Dincer; Caroline Connor


Files in this item

Thumbnail
Name:
Publisher version
Thumbnail
Name:
1_s2.0_S0920996412003544_main.pdf
Size:
800.2Kb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record