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

Abstract：

:Major 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 high-throughput 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 stress-susceptible 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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Wang J,Hodes GE,Zhang H,Zhang S,Zhao W,Golden SA,Bi W,Menard C,Kana V,Leboeuf M,Xie M,Bregman D,Pfau ML,Flanigan ME,Esteban-Fernández A,Yemul S,Sharma A,Ho L,Dixon R,Merad M,Han MH,Russo SJ,Pasinetti GM

doi

10.1038/s41467-017-02794-5

subject

Has Abstract

pub_date

2018-02-02 00:00:00

pages

477

issue

1

issn

2041-1723

pii

10.1038/s41467-017-02794-5

journal_volume

9

pub_type

杂志文章

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