Genetic predisposition to high anxiety- and depression-like behavior coincides with diminished DNA methylation in the adult rat amygdala.

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dc.contributor.authorMcCoy, Chelsea R.en
dc.contributor.authorJackson, Nateka L.en
dc.contributor.authorDay, Jeremyen
dc.contributor.authorClinton, Sarah M.en
dc.contributor.departmentSchool of Neuroscienceen
dc.coverage.spatialNetherlandsen
dc.date.accessioned2017-02-22T16:20:20Zen
dc.date.available2017-02-22T16:20:20Zen
dc.date.issued2017-03-01en
dc.description.abstractUnderstanding biological mechanisms that shape vulnerability to emotional dysfunction is critical for elucidating the neurobiology of psychiatric illnesses like anxiety and depression. To elucidate molecular and epigenetic alterations in the brain that contribute to individual differences in emotionality, our laboratory utilized a rodent model of temperamental differences. Rats bred for low response to novelty (Low Responders, LRs) are inhibited in novel situations and display high anxiety, helplessness, and diminished sociability compared to High Novelty Responder (HR) rats. Our current transcriptome profiling experiment identified widespread gene expression differences in the amygdala of adult HR/LR rats; we hypothesize that HR/LR gene expression and downstream behavioral differences stem from distinct epigenetic (specifically DNA methylation) patterning in the HR/LR brain. Although we found similar levels of DNA methyltransferase proteins in the adult HR/LR amygdala, next-generation sequencing analysis of the methylome revealed 793 differentially methylated genomic sites between the groups. Most of the differentially methylated sites were hypermethylated in HR versus LR, so we next tested the hypothesis that enhancing DNA methylation in LRs would improve their anxiety/depression-like phenotype. We found that increasing DNA methylation in LRs (via increased dietary methyl donor content) improved their anxiety-like behavior and decreased their typically high levels of Forced Swim Test (FST) immobility; however, dietary methyl donor depletion exacerbated LRs' high FST immobility. These data are generally consistent with findings in depressed patients showing that treatment with DNA methylation-promoting agents improves depressive symptoms, and highlight epigenetic mechanisms that may contribute to individual differences in risk for emotional dysfunction.en
dc.description.versionPublished versionen
dc.format.extent165 - 178 page(s)en
dc.identifier.doihttps://doi.org/10.1016/j.bbr.2016.12.008en
dc.identifier.eissn1872-7549en
dc.identifier.urihttp://hdl.handle.net/10919/75129en
dc.identifier.volume320en
dc.languageengen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/27965039en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAnxietyen
dc.subjectDNA methylationen
dc.subjectDepressionen
dc.subjectDieten
dc.subjectEpigeneticsen
dc.subjectMethyl depletionen
dc.titleGenetic predisposition to high anxiety- and depression-like behavior coincides with diminished DNA methylation in the adult rat amygdala.en
dc.title.serialBehavioural Brain Researchen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen

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