氯胺酮基于神经胶质细胞的非NMDARs抗抑郁机制研究进展
Research advances on non-related NMDARs antidepressant mechanisms of ketamine in glial cells
范亦博 1尚大瑾 1胡思颖 1徐晓明2
作者信息
- 1. 中国医科大学第一临床学院,辽宁沈阳 110122
- 2. 中国医科大学法医学院,辽宁沈阳 110122
- 折叠
摘要
氯胺酮是N-甲基-D-天冬氨酸离子型谷氨酸受体(NMDARs)拮抗剂,除了具有分离麻醉和镇痛作用外,还具有抗抑郁效果.本文对氯胺酮对神经胶质细胞相关的非NMDARs抗抑郁作用机制进行综述.结果显示,氯胺酮增加星形胶质细胞的脑源性神经营养因子(BDNF)表达水平,通过抑制Ca2+兴奋性和改变胆固醇分布而影响星形胶质细胞的囊泡-质膜的相互作用,调节星形胶质细胞K+的内稳态发挥抗抑郁作用.小胶质细胞相关机制包括氯胺酮促进小胶质细胞信号转导和转录激活因子3(STAT3)的表达、抑制小胶质细胞中的ROS和NLRP3通路、抑制TLR4/p38信号通路下调炎性细胞因子及通过下调P2X7表达抑制小胶质细胞活化.氯胺酮的少突胶质细胞相关抗抑郁机制与髓鞘的形成和修复有关.提高对氯胺酮的抗抑郁机制的理解有助于抑郁的诊疗水平的提升.
Abstract
As an antagonist of N-methyl-D-aspartate ionotropic glutamate receptors(NMDARs),ketamine has antidepres-sant and isolated anesthetic and analgesic effects.This review focused upon non-NMDARs related antidepressant mechanisms of ketamine in glial cells.Ketamine could boost the expression level of brain-derived neurotrophic factor(BDNF)in astrocytes,affect the vesicle plasma membrane interaction of astrocytes through suppressing Ca2+excitability and altering cholesterol distribu-tion.Also it was capable of regulating the homeostasis of K+in astrocytes and then exerting antidepressant effects.The mecha-nisms correlated with microglia include promoting the expression of signal transduction and transcription activating factor 3(STAT3)in microglia,arresting the NLRP3 pathways in microglia,down-regulating inflammatory cytokines through depressing the TLR4/p38 signaling pathway and blunting microglia activation through down-regulating P2X7 expression.The antidepressant mechanism of ketamine correlated with oligodendrocytes lies in the formation and repair of myelin sheath.Improving the under-standing of antidepressant mechanism of ketamine may contribute to a higher diagnostic and therapeutic level of depression.
关键词
氯胺酮/神经胶质细胞/脑源性神经营养因子/囊泡-质膜Key words
ketamine/glial cells/BDNF/vesicle-plasma membrane引用本文复制引用
基金项目
辽宁省大学生创新创业类资助项目(S202310159013)
出版年
2024
NETL
NSTL
万方数据