Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice.
Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice.
复制标题
炎症和突触可塑性的表观遗传调节促进小鼠对压力的恢复力。
DOI：
10.1038/s41467-017-02794-5
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发表时间：
2018-02-02
影响因子：
16.6
通讯作者：
Pasinetti GM
中科院分区：
文献类型：
--
作者：
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
重度抑郁症与大脑和免疫系统的异常有关。动物慢性应激研究表明，表观遗传和炎症机制在调节抑郁症的恢复力和易感性中起着重要作用。在这里，通过高通量筛选，我们确定了两种植物化学物质，二氢咖啡酸（DHCA）和锦葵素-3 ′-O-葡萄糖苷（Mal-gluc），它们通过调节大脑突触可塑性和外周炎症，有效地促进了对压力的恢复力。DHCA/Mal-gluc还显著降低了由移植来自应激敏感小鼠的造血祖细胞诱导的全身炎症增加的小鼠模型中的抑郁样表型。DHCA通过抑制富含CpG的IL-6序列内含子1和3的DNA甲基化来减少促炎性白细胞介素6（IL-6）的产生，而Mal-gluc通过增加Rac 1基因调控序列的组蛋白乙酰化来调节突触可塑性。外周炎症和突触适应不良符合新假设的抑郁症临床干预目标，目前可用的抗抑郁药无法解决。多酚类化合物具有部分抗抑郁作用，但机制不明。在这里，作者从生物活性膳食多酚中鉴定出两种植物化学物质，在啮齿动物抑郁模型中显示出其抗抑郁作用，并且这种作用是由表观遗传和抗炎机制介导的。
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. Polyphenols have partial antidepressant effect without known mechanism. Here, the authors identify two phytochemicals from bioactive dietary polyphenols, show their antidepressant effect in a rodent model of depression, and that this effect is mediated by epigenetic and anti-inflammatory mechanisms.
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DOI：
10.1523/jneurosci.1758-09.2009
发表时间：
2009-09-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Covington HE 3rd;Maze I;LaPlant QC;Vialou VF;Ohnishi YN;Berton O;Fass DM;Renthal W;Rush AJ 3rd;Wu EY;Ghose S;Krishnan V;Russo SJ;Tamminga C;Haggarty SJ;Nestler EJ
通讯作者：
Nestler EJ
DOI：
10.1126/science.1249240
发表时间：
2014-04-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Friedman AK;Walsh JJ;Juarez B;Ku SM;Chaudhury D;Wang J;Li X;Dietz DM;Pan N;Vialou VF;Neve RL;Yue Z;Han MH
通讯作者：
Han MH
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.8
作者：
Ho, Lap;Ferruzzi, Mario G.;Pasinetti, Giulio Maria
通讯作者：
Pasinetti, Giulio Maria
影响因子：
10.6
作者：
Dowlati, Yekta;Herrmann, Nathan;Lanctot, Krista L.
通讯作者：
Lanctot, Krista L.