Differential stress induced c-Fos expression and identification of region-specific miRNA-mRNA networks in the dorsal raphe and amygdala of high-responder/low-responder rats

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dc.contributor.authorCohen, Joshua L.en
dc.contributor.authorAta, Anoosha E.en
dc.contributor.authorJackson, Nateka L.en
dc.contributor.authorRahn, Elizabeth J.en
dc.contributor.authorRamaker, Ryne C.en
dc.contributor.authorCooper, Saraen
dc.contributor.authorKerman, Ilan A.en
dc.contributor.authorClinton, Sarah M.en
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentSchool of Neuroscienceen
dc.date.accessioned2017-02-22T16:24:25Zen
dc.date.available2017-02-22T16:24:25Zen
dc.date.issued2017-02en
dc.description.abstractChronic stress triggers a variety of physical and mental health problems, and how individuals 2 cope with stress influences risk for emotional disorders. To investigate molecular mechanisms 3 underlying distinct stress coping styles, we utilized rats that were selectively-bred for differences 4 in emotionality and stress reactivity. We show that high novelty responding (HR) rats readily 5 bury a shock probe in the defensive burying test, a measure of proactive stress coping behavior, 6 while low novelty responding (LR) rats exhibit enhanced immobility, a measure of reactive 7 coping. Shock exposure in the defensive burying test elicited greater activation of HR rats’ 8 caudal dorsal raphe serotonergic cells compared to LRs, but lead to more pronounced 9 activation throughout LRs’ amygdala (lateral, basolateral, central, and basomedial nuclei) 10 compared to HRs. RNA-sequencing revealed 271 mRNA transcripts and 33 microRNA species 11 that were differentially expressed in HR/LR raphe and amygdala. We mapped potential 12 microRNA-mRNA networks by correlating and clustering mRNA and microRNA expression and 13 identified networks that differed in either the HR/LR dorsal raphe or amygdala. A dorsal raphe 14 network linked three microRNAs which were down-regulated in LRs (miR-206-3p, miR-3559-5p, 15 and miR-378a-3p) to repression of genes related to microglia and immune response (Cd74, 16 Cyth4, Nckap1l, and Rac2), the genes themselves were up-regulated in LR dorsal raphe. In the 17 amygdala, another network linked miR-124-5p, miR-146a-5p, miR-3068-3p, miR-380-5p, miR-18 539-3p, and miR-7a-1-3p with repression of chromatin remodeling-related genes (Cenpk, 19 Cenpq, Itgb3bp, and Mis18a). Overall this work highlights potential drivers of gene-networks 20 and downstream molecular pathways within the raphe and amygdala that contribute to 21 individual differences in stress coping styles and stress vulnerabilities.en
dc.description.notespublisher: Elsevier articletitle: Differential stress induced c-Fos expression and identification of region-specific miRNA-mRNA networks in the dorsal raphe and amygdala of high-responder/low-responder rats journaltitle: Behavioural Brain Research articlelink: http://dx.doi.org/10.1016/j.bbr.2016.11.015 content_type: article copyright: © 2016 Elsevier B.V. All rights reserved.en
dc.description.versionPublished versionen
dc.format.extent110 - 123 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.bbr.2016.11.015en
dc.identifier.issn0166-4328en
dc.identifier.orcidClinton, SM [0000-0001-7158-411X]en
dc.identifier.urihttp://hdl.handle.net/10919/75130en
dc.identifier.volume319en
dc.language.isoenen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.titleDifferential stress induced c-Fos expression and identification of region-specific miRNA-mRNA networks in the dorsal raphe and amygdala of high-responder/low-responder ratsen
dc.title.serialBehavioural Brain Researchen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
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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