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

Jun Wang, Georgia E. Hodes, Hongxing Zhang, Song Zhang, Wei Zhao, Sam A. Golden, Weina Bi, Caroline Menard, Veronika Kana, Marylene Leboeuf, Marc Xie, Dana Bregman, Madeline L. Pfau, Meghan E. Flanigan, Adelaida Esteban-Fernández, Shrishailam Yemul, Ali Sharma, Lap Ho, Richard Dixon, Miriam Merad, Ming-Hu Han, Scott J. Russo and Giulio M. Pasinetti ()
Additional contact information
Jun Wang: Icahn School of Medicine at Mount Sinai
Georgia E. Hodes: Icahn School of Medicine at Mount Sinai
Hongxing Zhang: Icahn School of Medicine at Mount Sinai
Song Zhang: Icahn School of Medicine at Mount Sinai
Wei Zhao: Icahn School of Medicine at Mount Sinai
Sam A. Golden: Icahn School of Medicine at Mount Sinai
Weina Bi: Icahn School of Medicine at Mount Sinai
Caroline Menard: Icahn School of Medicine at Mount Sinai
Veronika Kana: Icahn School of Medicine at Mount Sinai
Marylene Leboeuf: Icahn School of Medicine at Mount Sinai
Marc Xie: Icahn School of Medicine at Mount Sinai
Dana Bregman: Icahn School of Medicine at Mount Sinai
Madeline L. Pfau: Icahn School of Medicine at Mount Sinai
Meghan E. Flanigan: Icahn School of Medicine at Mount Sinai
Adelaida Esteban-Fernández: Icahn School of Medicine at Mount Sinai
Shrishailam Yemul: Icahn School of Medicine at Mount Sinai
Ali Sharma: Icahn School of Medicine at Mount Sinai
Lap Ho: Icahn School of Medicine at Mount Sinai
Richard Dixon: University of North Texas
Miriam Merad: Icahn School of Medicine at Mount Sinai
Ming-Hu Han: Icahn School of Medicine at Mount Sinai
Scott J. Russo: Icahn School of Medicine at Mount Sinai
Giulio M. Pasinetti: Icahn School of Medicine at Mount Sinai

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02794-5

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DOI: 10.1038/s41467-017-02794-5

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