《生命科学》 2024, 36(7): 917-928

脑内特定基因DNA甲基化在焦虑症中的生物学机制

张文欣^1,2 , 闫文静^1,2 , 王　月^1,2 , 刘怀玉^1,2 , 李米亚^1,2 , 何　治^1,2,3,*

¹三峡大学国家中医药管理局中药药理科研三级实验室，宜昌 443002 ²三峡大学健康医学院，宜昌 443002 ³嘉兴大学医学院，嘉兴 314000

摘　要：

焦虑症是一种常见的精神障碍性疾病。DNA 甲基化是焦虑症发展中关键的表观遗传学机制，其能够在不改变DNA 序列的前提下改变遗传表型，并通过DNA 甲基转移酶的作用在基因组CpG 二核苷酸的胞嘧啶5 号碳位共价键结合一个甲基基团，抑制基因转录、影响染色质结构和调节组蛋白修饰，从而影响基因表达。焦虑症动物模型的相关大脑区域中DNA 甲基化水平发生改变，影响基因表达和神经递质调节等生物学过程，但DNA 甲基化在焦虑中的作用机制尚不完全清楚。本文主要阐述脑内特定基因，如糖皮质激素受体(GR) 基因、脑源性神经营养因子(BDNF) 基因以及5- 羟色胺(5-HT) 相关基因的甲基化与焦虑症之间的关系，并总结研究进展和提出相应见解，旨在为焦虑症的预防和治疗提供理论依据。

通讯作者：何　治 , Email:z15672728215@163.com

Biological mechanisms of DNA methylation of brain specific genes in anxiety disorders

ZHANG Wen-Xin^1,2 , YAN Wen-Jing^1,2 , WANG Yue^1,2 , LIU Huai-Yu^1,2 , LI Mi-Ya^1,2 , HE Zhi^1,2,3,*

¹Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China ²Health Medical College, China Three Gorges University, Yichang 443002, China ³Jiaxing University School of Medicine, Jiaxing 314000, China

Abstract:

Anxiety disorder is a common mental disorder. DNA methylation is a key epigenetic mechanism in the  development of anxiety disorders, which can alter genetic expression without altering the DNA sequence and binds  a methyl group to the cytosine 5 carbon of CpG dinucleotide through the action of DNA methyltransferase, thereby inhibiting gene transcription, affecting chromatin structure, and regulating histone modification in ways to affect gene expression. Animal models of anxiety disorders involve mechanisms by which altered levels of DNA  methylation in relevant brain regions affect gene expression and regulate neurotransmitters. The mechanism of  action of DNA methylation in anxiety is not fully understood. This paper focuses on the relationship between DNA  methylation of brain specific genes, such as glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF)  and 5-hydroxytryptamine (5-HT) related gene and anxiety disorders, and summarizes the research and puts forward corresponding opinions, aiming at providing theoretical basis for the prevention and treatment of anxiety disorders.

Communication Author：HE Zhi , Email:z15672728215@163.com