Relationship between BDNF and SLC6A4 Gene Methylation and the Prognosis of Stroke

doi:10.3969/j.issn.1673-5765.2022.11.004

Abstract

Abstract: Previous studies have shown that the brain-derived neurotrophic factor (BDNF) gene and serotonin reuptake transporter coding gene (SLC6A4) may play an important role in improving the clinical prognosis of stroke through several approaches, and their expression are regulated by DNA methylation. Methylation of BDNF promoter will lead to the decrease of BDNF, which can affect post-stroke functional recovery through inhibiting cell adhesion, proliferation, angiogenesis and other mechanisms; BDNF methylation is related to neuroplasticity, which may explain its effect on post-stroke rehabilitation; BDNF methylation may enhance the fear reflex in the amygdala and hippocampus, resulting in stroke patients more prone to anxiety and depression. Hypermethylation of SLC6A4 promoter may lead to the 5-HT axis dysfunction, which promotes cerebral and peripheral platelet aggregation and local vasoconstriction, thus increasing the risk of cardio-cerebrovascular events; and SLC6A4 methylation may affect stroke rehabilitation by affecting motor cortex excitability, neuroplasticity and the release of inflammatory factors and immune mediators; and it may be related to post-stroke depression by affecting the plasticity of hippocampal neurons and the balance of kynurenine axis and hypothalamic-pituitary-adrenal (HPA) axis. This article mainly reviewed the effect of methylation of BDNF and SLC6A4 genes on the prognosis of stroke and the possible mechanism.

Key words: BDNF; SLC6A4; DNA methylation; Stroke

摘要： DNA甲基化与卒中预后相关。脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）基因及血清素再摄取转运体编码基因——溶质载体家族6成员4（solute carrier family 6，member 4，SLC6A4）基因表达均受到DNA甲基化调控，可能通过多种途径在改善卒中患者的临床预后方面发挥重要作用。BDNF基因启动子区域的甲基化会导致BDNF的合成减少，从而通过抑制细胞黏附、细胞增殖、血管生成等多种机制影响卒中后的功能恢复；BDNF基因甲基化与神经可塑性相关，这可能解释其对卒中后康复治疗的影响；BDNF基因甲基化使杏仁核和海马体对恐惧的反射增强，导致卒中患者更容易出现焦虑、抑郁症状。SLC6A4基因启动子区域高甲基化水平可能导致5-羟色胺能轴调节障碍，进而促进大脑和外周血小板聚集和局部血管收缩，增加心脑血管事件的复发风险；SLC6A4基因甲基化可能通过影响运动皮质兴奋性、神经元可塑性以及影响炎症因子和免疫介质的释放，影响卒中后康复；同时可能通过影响海马神经元的可塑性以及犬尿氨酸轴、下丘脑-垂体-肾上腺轴的平衡与卒中后抑郁的发生相关。本文主要通过综述既往相关研究，重点介绍BDNF和SLC6A4基因甲基化对卒中预后的影响以及可能的作用机制。

关键词: 脑源性神经营养因子; 血清素再摄取转运体编码基因; DNA甲基化; 卒中

YAN Ran, MIN Yan, QUAN Kehua, LI Zixiao. Relationship between BDNF and SLC6A4 Gene Methylation and the Prognosis of Stroke [J]. Chinese Journal of Stroke, 2022, 17(11): 1178-1182.

闫然, 闵妍, 全柯华, 李子孝. 脑源性神经营养因子和血清素再摄取转运体编码基因甲基化与卒中预后的关系[J]. 中国卒中杂志, 2022, 17(11): 1178-1182.

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