江苏大学学报（医学版）2026，Vol.36Issue(2)：100-104,5.DOI:10.13312/j.issn.1671-7783.y250095
阿尔茨海默病小鼠海马脑区PGC-1α阳性神经元活化模型的构建
Construction of a model of activated PGC-1α positive neurons in the hippocampus of Alzheimer's disease mice
摘要
Abstract
Objective:To establish a optogenetic model of peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)activation in the hippocampal neurons of Alzheimer's disease(AD)mice.Methods:Twenty-four APP/PS1 double transgenic(AD model)mice were selected and randomly divided into 4 groups based on the type of viral intervention(AAV-Ppargc1α-hChR2/AAV-Control-hChR2)and light treatment(light stimulation/no light stimulation):AD+AAV-Control-hChR2+no light stimulation group,AD+AAV-Control-hChR2+light stimulation group,AD+AAV-Ppargc1α-hChR2+no light stimulation group,and AD+AAV-Ppargc1α-hChR2+light stimulation group,with 6 in each group.Genotypes were confirmed by PCR.Adeno-associated virus carrying the light-sensitive protein hChR2 was microinjected into the dentate gyrus of the hippocampus of AD mice,and optical fibers were implanted at the injection site.Two weeks after viral expression,blue light stimulation was applied at 5-minute intervals lasting for 30 seconds each,for 2 hours a day,for 5 days.Immunofluorescence was used to detect the number of Cfos+HA+cells in the hippocampus of the four groups of mice to verify the effectiveness of the light-sensitive protein;immunofluorescence was also used to detect the number of PGC-1α positive neurons in the hippocampus of AD mice under the same light stimulation conditions.Results:PCR results showed that mice with both APP and PS1 bands were AD double transgenic mice.Compared with the no light stimulation groups(AD+AAV-Control-hChR2+no light stimulation and AD+AAV-Pgc-1α-hChR2+no light stimulation),the number of Cfos+HA+neurons in the hippocampus of the light stimulation groups(AD+AAV-Control-hChR2+light stimulation and AD+AAV-Pgc-1α-hChR2+light stimulation)increased significantly(P＜0.01).Compared with AAV-Control-hChR2+light stimulation group,the expression of PGC-1α positive neurons in the hippocampus of AD mice in AAV-Pgc-1α-hChR2+light stimulation group was significantly increased(t=9.613,P＜0.01).Conclusion:A hippocampus-specific optogenetic model for PGC-1α activation in AD mice was successfully established.关键词
阿尔茨海默病/光遗传学/过氧化物酶体增殖物激活受体γ辅激活因子-1α/海马Key words
Alzheimer's disease/optogenetics/peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)/hippocampus分类
医药卫生引用本文复制引用
王贻界,朱旭,康子涵,邹成智,王佳庆,潘雯,王佳,刘凤国..阿尔茨海默病小鼠海马脑区PGC-1α阳性神经元活化模型的构建[J].江苏大学学报（医学版）,2026,36(2):100-104,5.基金项目
江苏省中医药科技发展计划面上项目(MS2025107) （MS2025107）
江苏省检验医学重点实验室开放课题(JSKLM-Y-2025-15) （JSKLM-Y-2025-15）
