南方医科大学学报2025，Vol.45Issue(3)：506-513,8.DOI:10.12122/j.issn.1673-4254.2025.03.08
金丝桃素通过调节小鼠小胶质细胞内CN-NFAT钙信号通路改善压力应激诱导的抑郁样行为
Hypericin ameliorates stress-induced depressive-like behaviors in mice by modulating the CN-NFAT calcium signaling pathway in microglia
摘要
Abstract
Objective To investigate the role of the calcium/calmodulin(CaM)-mediated activation of calcineurin(CN)-nuclear factor of activated T cells(NFAT)signaling pathway in mediating the regulatory effect of hyperforin(HY)on stress-induced depression-like disorder(DP)in mice.Methods C57BL/6J mice were randomly divided into control group,DP model group,and hyperforin treatment group(n=15).Behavioral changes of the mice were assessed using open field test(OFT),sucrose preference test(SPT),tail suspension test(TST),light/dark box test(LDB),and novel object suppression test(NSFT).Immunohistochemistry was used to detect tyrosine hydroxylase(TH)expression in the CA1 region of the hippocampus,and serum serotonin(5-HT)and norepinephrine(NA)levels were detected with ELISA.Western blotting was used to analyze the expressions of TNF-α,IL-1β,IL-2,and CN-NFAT pathway proteins.In cultured BV-2 microglial cells with lipopolysaccharide(LPS)stimulation,the effects of hyperforin and CN inhibitor(CNIS)on expressions of ionized calcium-binding adapter molecule 1(IBA-1),5-HT,NA,inflammatory cytokines and CN-NFAT pathway proteins were examined using immunofluorescence assay,ELISA or Western blotting.Results Compared with the control mice,the mice in DP group showed significantly reduced activity in OFT,decreased sucrose consumption in SPT,reduced shuttle crossing in LDB,and lowered food intake in NSFT with significantly increased immobility in TST.The mice with DP showed significantly decreased TH-positive neurons,lowered 5-HT and NA levels,and increased expressions of TNF-α,IL-1β,IL-2 and CaM-CN-NFAT pathway proteins.In cultured BV-2 cells,LPS stimulation strongly increased cellular IBA-1 expression,decreased the levels of neurotransmitters(5-HT and NA),and increased the levels of inflammatory cytokines and CN-NFAT signaling,and these changes were effectively reversed by treatment with hyperforin or CNIS.Conclusion Hyperforin improves stress-induced depression-like behaviors in mice and activated BV-2 cells by targeting the CN-NFAT signaling pathway.关键词
金丝桃素/压力应激/CN-NFAT信号通路/脂多糖/抑郁Key words
hypericin/stress due to pressure/CN-NFAT signaling pathway/lipopolysaccharide/depression引用本文复制引用
高正涛,许茜,林萍燕,周炳灿,陈明恒,刘尔祺,雷添翔,倪慧心,刘海鑫,林瑶..金丝桃素通过调节小鼠小胶质细胞内CN-NFAT钙信号通路改善压力应激诱导的抑郁样行为[J].南方医科大学学报,2025,45(3):506-513,8.基金项目
国家自然科学基金青年项目(81904263) （81904263）
福建省自然科学基金面上项目(2024J01745、2024J01123) （2024J01745、2024J01123）
福建中医药大学中医健康管理学联合省级临床重点专科建设项目(老年病科)(XJG2023018) （老年病科）
福建中医药大学校管课题青年项目(X2023010) （X2023010）
福建中医药大学校管课题(X2024029) （X2024029）
福建省"大学生创新创业训练计划"项目校级立项 Supported by Youth Program of National Natural Science Foundation of China(81904263). （81904263）
