南方医科大学学报2024，Vol.44Issue(5)：810-817,8.DOI:10.12122/j.issn.1673-4254.2024.05.02
辅酶Q10通过下调焦亡信号通路缓解抑郁小鼠的抑郁样行为
Coenzyme Q10 alleviates depression-like behaviors in mice with chronic restraint stress by down-regulating the pyroptosis signaling pathway
摘要
Abstract
Objective To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress(CRS).Methods Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low,moderate and high doses(50,100 and 200 mg/kg,respectively,n=8),VX765(a caspase-1 specific inhibitor,50 mg/kg,n=8),or fluoxetine(10 mg/kg,n=8)on a daily basis for 4 weeks,and the changes in depression-like behaviors of the mice were assessed by sugar water preference test,forced swimming test and tail suspension test.The expression of glial fibrillary acidic protein(GFAP)in the hippocampus of the mice was detected using immunohistochemistry,and the number of synaptic spines was determined with Golgi staining.Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus,and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay.Results Compared with the normal control mice,the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests(P<0.05),and these depression-like behaviors were obviously improved by treatment with coenzyme Q10,VX765 or FLX.The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines,enhanced expressions of GSDMD-N,caspase-1 and IL-1β,and increased colocalization of neurons and caspase-1 p10(all P<0.05).All these changes were significantly ameliorated in the mouse models after treatment with Q10.Conclusion Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.关键词
慢性应激束缚模型/抑郁症/辅酶Q10/caspase-1/焦亡Key words
chronic restraint stress/depression/coenzyme Q10/caspase-1/pyroptosis引用本文复制引用
孙一鸣,张荣,孟莹,朱磊,李明强,刘哲..辅酶Q10通过下调焦亡信号通路缓解抑郁小鼠的抑郁样行为[J].南方医科大学学报,2024,44(5):810-817,8.基金项目
国家自然科学基金(82104152) （82104152）
安徽省高校自然科学研究重点项目(KJ2021A0778) （KJ2021A0778）
蚌埠医学院大学生创新项目(S202310367122) Supported by National Natural Science Foundation of China(82104152). （S202310367122）
