Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice

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dc.contributor.authorWang, Junen
dc.contributor.authorHodes, Georgia E.en
dc.contributor.authorZhang, Hongxingen
dc.contributor.authorZhang, Songen
dc.contributor.authorZhao, Weien
dc.contributor.authorGolden, Sam A.en
dc.contributor.authorBi, Weinaen
dc.contributor.authorMenard, Carolineen
dc.contributor.authorKana, Veronikaen
dc.contributor.authorLeboeuf, Maryleneen
dc.contributor.authorXie, Marcen
dc.contributor.authorBregman, Danaen
dc.contributor.authorPfau, Madeline L.en
dc.contributor.authorFlanigan, Meghan E.en
dc.contributor.authorEstebam-Fernández, Adelaidaen
dc.contributor.authorYemul, Shrishailamen
dc.contributor.authorSharma, Alien
dc.contributor.authorHo, Lapen
dc.contributor.authorDixon, Richard A.en
dc.contributor.authorMerad, Miriamen
dc.contributor.authorHan, Ming-Huen
dc.contributor.authorRusso, Scott J.en
dc.contributor.authorPasinetti, Giulio M.en
dc.date.accessioned2018-04-18T12:50:11Zen
dc.date.available2018-04-18T12:50:11Zen
dc.date.issued2018en
dc.description.abstractMajor depressive disorder is associated with abnormalities in the brain and the immune system. Chronic stress in animals showed that epigenetic and inflammatory mechanisms play important roles in mediating resilience and susceptibility to depression. Here, through a highthroughput screening, we identify two phytochemicals, dihydrocaffeic acid (DHCA) and malvidin-3′-O-glucoside (Mal-gluc) that are effective in promoting resilience against stress by modulating brain synaptic plasticity and peripheral inflammation. DHCA/Mal-gluc also significantly reduces depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of hematopoietic progenitor cells from stresssusceptible mice. DHCA reduces pro-inflammatory interleukin 6 (IL-6) generations by inhibiting DNA methylation at the CpG-rich IL-6 sequences introns 1 and 3, while Mal-gluc modulates synaptic plasticity by increasing histone acetylation of the regulatory sequences of the Rac1 gene. Peripheral inflammation and synaptic maladaptation are in line with newly hypothesized clinical intervention targets for depression that are not addressed by currently available antidepressants.en
dc.identifier.doihttps://doi.org/10.1038/s41467-017-02794-5en
dc.identifier.urihttp://hdl.handle.net/10919/82845en
dc.identifier.volume9en
dc.language.isoen_USen
dc.publisherNatureen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.titleEpigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in miceen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden

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Destination Area: Adaptive Brain and Behavior (ABB)