miR-124在抑郁症中的作用机制  

The Mechanism of miR-124 in Depression

作　　者：薛燕 李德珠 谢慧莹 蒋传邈 张俊芳[1,2] XUE Yan;LI De-Zhu;XIE Hui-Ying;JIANG Chuan-Miao;ZHANG Jun-Fang(Health Science Center,Ningbo University,Zhejiang Provincial Key Laboratory of Pathophysiology,Ningbo 315211,China;The Affiliated Kangning Hospital of Ningbo University,Ningbo 315201,China)

机构地区：[1]宁波大学医学部,浙江省病理生理学技术研究重点实验室,宁波315211 [2]宁波大学附属康宁医院,宁波315201

出　　处：《生物化学与生物物理进展》2024年第6期1316-1326,共11页Progress In Biochemistry and Biophysics

基　　金：浙江省自然科学基金(LY23H090003);宁波市公益性科技计划项目(2022S021);海洋生物医药创新学科引智基地(国家111计划,D16013);宁波大学大学生科技创新项目(2023SRIP1934);王宽诚基金资助。

摘　　要：抑郁症是世界范围内最常见的精神疾病之一,发病机制复杂,研究仍处于探索阶段。微RNA(miRNA)作为表观遗传机制的重要调控因子,在抑郁症的发生发展中起着重要作用。miR-124是神经系统中表达最丰富的miRNA之一,参与了神经元分化、小胶质细胞激活等生物事件。近年研究表明,miR-124在抑郁症患者和动物模型中表达异常,并参与了病理生理机制。然而,miR-124的表达异常情况及其相关机制的研究结果是较复杂的、甚至矛盾的。故本文对此进行梳理,总结了miR-124在抑郁症中的研究进展。Depression is a prevalent mental illness worldwide,its multifaceted pathogenesis is still in the exploratory stage.MicroRNA(miRNA),as a crucial epigenetic regulator,plays an important role in depression.miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia,and involved in various biological events like neuron development and differentiation,synaptic and axonal growth,neural plasticity,inflammation and autophagy.Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models.Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS,CSDS,CORT,CRS and LH but some evidence for divergence.Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway,GR pathway,SIRT1 pathway,apoptosis and autophagy pathways by directly targeting these genes including Creb,Bdnf,Sirt1,Nr3c1,Ezh2 and Stat3.The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway.The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models,and resulted in neuroinflammation.In summary,the abnormal expression of miR-124 in the brain of depressionrelated models and its related mechanisms are complex and even contradictory,and still need further research.This review provides a summary of the research progress of miR-124 in depression.

关 键 词：抑郁症 miR-124 海马 糖皮质激素受体 神经发生 神经炎症 

分 类 号：Q752[生物学—分子生物学] R749.4[医药卫生—神经病学与精神病学]