中国药理学通报2024，Vol.40Issue(8)：1523-1532,10.DOI:10.12360/CPB202411077
柴金解郁安神片调控CaMKII和Cofilin双信号通路改善抑郁症海马谷氨酸能神经元突触重塑
Chaijin Jieyu Anshen tablets regulating CaMKII and Cofilin dual signal pathway alleviate synaptic remodeling of glutaminergic hippocampal neurons in depression
摘要
Abstract
Aim To reveal the mechanism of Chaijin Jieyu Anshen tablets(CJJYAS)regulating CaMKII and Cofilin dual signal pathway to improve synaptic remod-eling of glutaminergic hippocampal neurons in depres-sion.Methods The cell model of depression was es-tablished by corticosterone and lipopolysaccharide.The cells were randomly divided into the control group,model group,GR blocker group,GR agonist group,CX3CR1 blockergroup,CX3CR1 agonist group,CJJ-YAS group,CJJYAS combined with GR agonist group,and CJJYAS combined with CX3CR1 agonist group.Cell imaging analysis was used to observe the morpho-logical and structural changes of astrocytes,microglia,anterior cingulate cortex(ACC)and hippocampal(HPC)glutaminergic neurons.Immunofluorescence was used to test the activation of ACC and HPC glu-taminergic neurons and synaptic remodeling.Immuno-fluorescence and Western blot were respectively used to detect the expressions of synaptic remodeling-related proteins N-methyl-D-asprtate receptor 2A(GRIN2A),GRIN2B,CaMKII,MK2 and Cofilin in HPC glutamin-ergic neurons.Results CJJYAS could significantly improve the morphological and structural damage of as-trocytes,microglia,ACC and HPC neurons.Further-more,CJJYAS markedly restrained the excessive acti-vation of ACC and HPC glutaminergic neurons and the hippocampal synaptic plasticity damage and synaptic remodeling via down-regulating GRIN2A,GRIN2B and MK2 proteins,and up-regulating CaMKII and Cofilin protein.Conclusions CJJYAS effectively alleviate the synaptic remodeling of glutaminergic hippocampal neurons in depression,and its molecular mechanism might be associated with the regulation of synapse-re-lated NR/CaMKII and MK2/Cofilin signaling path-ways.关键词
抑郁症/谷氨酸能神经元/突触重塑/NR/CaMKII/MK2/Cofilin/柴金解郁安神片Key words
depression/glutaminergic neurons/syn-aptic remodeling/NR/CaMKII/MK2/Cofilin/Chaijin Jieyu Anshen tablets分类
医药卫生引用本文复制引用
刘检,唐林,赵洪庆,刘林,杨蕙,李薇,孟盼,王宇红..柴金解郁安神片调控CaMKII和Cofilin双信号通路改善抑郁症海马谷氨酸能神经元突触重塑[J].中国药理学通报,2024,40(8):1523-1532,10.基金项目
国家重大新药创制科技重大专项资助项目(No 2017ZX09309026) （No 2017ZX09309026）
国家自然科学基金资助项目(No 82104793) （No 82104793）
湖南省自然科学基金资助项目(No 2022JJ30451) （No 2022JJ30451）
湖南省卫健委科研计划项目(No W20243072) （No W20243072）
湖南省三尖创新人才"湖湘青年英才"项目(No.2022RC1226) （No.2022RC1226）
