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二甲双胍通过调节 DNA 羟甲基化发挥抗抑郁作用。

Metformin exerts antidepressant effects by regulated DNA hydroxymethylation.

机构信息

Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu, China.

Institute of Neuroscience, Soochow University, Suzhou City, China.

出版信息

Epigenomics. 2019 May;11(6):655-667. doi: 10.2217/epi-2018-0187. Epub 2019 Feb 13.

DOI:10.2217/epi-2018-0187
PMID:30760033
Abstract

We aim to study the antidepressant mechanism of metformin. Tail suspension test and forced swimming test were used to detect the depression-like behavior; the expressions of target protein were examined by western blot; the levels of target genes were tested by quantitative PCR; the content of α-ketoglutarate and 5hmC were detected by ELISA kit. We showed that metformin can improve the depression-like behavior in spatial restraint stress model; then we found that metformin through AMPK/Tet2 pathway increasing the expression of BDNF to antidepression. Our study provided evidences that metformin plays a role of antidepressant effects through the AMPK/Tet2/BDNF pathway.

摘要

我们旨在研究二甲双胍的抗抑郁机制。采用悬尾试验和强迫游泳试验检测抑郁样行为;通过 Western blot 检测靶蛋白的表达;通过 qPCR 检测靶基因的水平;通过 ELISA 试剂盒检测 α-酮戊二酸和 5hmC 的含量。结果表明,二甲双胍可改善空间束缚应激模型中的抑郁样行为;然后我们发现二甲双胍通过 AMPK/Tet2 通路增加 BDNF 的表达来抗抑郁。本研究为二甲双胍通过 AMPK/Tet2/BDNF 通路发挥抗抑郁作用提供了证据。

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