2. Academic Validation
  3. The antidepressant effects of protein arginine methyltransferase 2 involve neuroinflammation

The antidepressant effects of protein arginine methyltransferase 2 involve neuroinflammation

  • Neurochem Int. 2024 Jun:176:105728. doi: 10.1016/j.neuint.2024.105728.
Shunfeng Liu 1,  Bei Zhang 2,  Haowei Guo 3,  Zhanghua Ding 4,  Wenhui Hou 5,  Xiaoli Hu 6,  Yuchu Wang 7,  Wupeng Tan 8,  Shouhong Zhou 9
Affiliations

Affiliations

  • 1 College of Pharmacy, Guilin Medical College, Guilin, 541199, China; Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541199, China. Electronic address: a531183@163.com.
  • 2 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541199, China; Basic Medical College, Guilin Medical College, Guilin, 541199, China. Electronic address: z18738356360@163.com.
  • 3 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541199, China; Basic Medical College, Guilin Medical College, Guilin, 541199, China. Electronic address: ghw155671@163.com.
  • 4 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541199, China; Basic Medical College, Guilin Medical College, Guilin, 541199, China. Electronic address: jgahting@163.com.
  • 5 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541199, China; Basic Medical College, Guilin Medical College, Guilin, 541199, China. Electronic address: 18778350358@163.com.
  • 6 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541199, China; Basic Medical College, Guilin Medical College, Guilin, 541199, China. Electronic address: 13298588356@163.com.
  • 7 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541199, China; Basic Medical College, Guilin Medical College, Guilin, 541199, China. Electronic address: 19178306392@163.com.
  • 8 Department of Gynaecology, Maternal and Child Health Hospital of Hengyang, Hengyang, 421001, China. Electronic address: tanwupeng@126.com.
  • 9 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541199, China; Basic Medical College, Guilin Medical College, Guilin, 541199, China. Electronic address: zhoushouhong@126.com.
PMID: 38561150 DOI: 10.1016/j.neuint.2024.105728
Abstract

Protein arginine methyltransferase (PRMT) 2 catalyzes the methylation of arginine residues in histones. Depression is associated with histone methylation; however, more comprehensive research is needed on how PRMT2 regulates depression. The present study aimed to investigate the effects and possible mechanism(s) of PRMT2 overexpression on depression-like behavior induced by chronic unpredictable mild stress (CUMS) in rats, and whether lentivirus-mediated PRMT2 overexpression in the hippocampus suppresses depression-like behavior. Furthermore, the PRMT2 inhibitor MS023 was administered to the Animals to investigate whether the antidepressant effect of PRMT2 overexpression could be reversed. Behavioral experiments were performed to detect depression-like behavior in rats. Western blotting was used to determine protein expression levels of PRMT2, histone H3R8 asymmetric dimethylation (H3R8me2a), inducible nitric oxide synthase (iNOS), and Arginase 1 (Arg1) in rat hippocampal tissues. Hippocampal microglia and PRMT2 were stained using immunofluorescence techniques. Enzyme-linked immunosorbent assay was used to determine the levels of various inflammatory factors in rat hippocampal tissue. Results of analysis revealed that PRMT2 overexpression in the hippocampus exerted an antidepressant effect. PRMT2 overexpression in the hippocampus reduced the proportion of activated microglia in the hippocampus, upregulated Arg1 and H3R8me2a expression, and downregulated iNOS expression. PRMT2 overexpression in the hippocampus inhibited the release of pro-inflammatory factors and promoted the release of anti-inflammatory factors. In summary, PRMT2 overexpression in the hippocampus promoted the conversion of microglia from the M1 to M2 type, resulting in an antidepressant effect. These results suggest that PRMT2 may be a potential therapeutic target to prevent and treat depression.

Keywords

Depression; Microglia; Neuroinflammation; PRMT2.

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