Chaijin Jieyu Anshen tablets regulating CaMKII and Cofilin dual signal pathway alleviate synaptic remodeling of glutaminergic hippocampal neurons in depression
- VernacularTitle: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
- Author:
Jian LIU
1
;
Lin TANG
;
Hong-Qing ZHAO
;
Lin LIU
;
Hui YANG
;
Wei LI
;
Pan MENG
;
Yu-Hong WANG
Author Information
- Keywords: depression; glutaminergic neurons; syn-aptic remodeling; NR/CaMKII; MK2/Cofilin; Chaijin Jieyu Anshen tablets
- From: Chinese Pharmacological Bulletin 2024;40(8):1523-1532
- CountryChina
- Language:Chinese
- 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.
