视神经萎缩蛋白-1对抑郁小鼠海马神经元凋亡及线粒体功能影响  

The effect of optical atrophy-1 on hippocampal neuronal apoptosis and mitochondrial function in depressed mice

作　　者：王奇 徐天朝 崔刚 董晓梅 宫莉莉 WANG Qi;XU Tian-chao;CUI Gang;DONG Xiao-mei;GONG Li-li(Department of Psychiatry and Psychology,General Hospital of Northern Theater Command,Shenyang 110016,China)

机构地区：[1]北部战区总医院精神心理科,辽宁沈阳110016

出　　处：《临床军医杂志》2024年第9期902-906,共5页Clinical Journal of Medical Officers

基　　金：辽宁省应用基础研究计划联合计划项目(2022JH2/101500040)。

摘　　要：目的探讨过表达视神经萎缩蛋白-1(OPA1)对抑郁小鼠海马神经元凋亡及线粒体功能的影响。方法将32只C57BL/6J小鼠随机分为对照组(CON组)、慢性应激组(CMS组)、慢性应激+空载体组(CMS+NC组)、慢性应激+OPA1过表达载体组(CMS+OPA1 OE组)。采用慢性应激建立抑郁模型,应激持续3周,随后对CMS+NC组和CMS+OPA1 OE组小鼠侧脑室分别注射对照病毒和过表达OPA1慢病毒。注射前及注射后1周,用糖水偏好实验、悬尾实验评估抑郁样行为,行为实验后进行分子生物学检测。结果慢病毒干预后,CMS+OPA1 OE组糖水偏好百分比高于CMS组、CMS+NC组,CMS+OPA1 OE组悬尾不动时间低于CMS组、CMS+NC组,差异均有统计学意义(P<0.05)。CMS组、CMS+NC组小鼠海马组织神经元凋亡率和Caspase-3阳性细胞表达率均高于CON组,CMS+OPA1 OE组小鼠海马组织神经元凋亡率和Caspase-3阳性细胞表达率均低于CMS组及CMS+NC组,差异均有统计学意义(P<0.05)。CMS组、CMS+NC组小鼠海马组织线粒体融合蛋白MFN1、MFN2表达水平均低于CON组,CMS+OPA1 OE组小鼠海马组织MFN1、MFN2表达水平均高于CMS组、CMS+NC组,差异均有统计学意义(P<0.05)。CMS组和CMS+NC组小鼠海马组织腺嘌呤核苷三磷酸(ATP)水平均低于CON组,CMS+OPA1 OE组ATP水平高于CMS组及CMS+NC组,差异均有统计学意义(P<0.05)。结论抑郁小鼠海马OPA1表达水平下降,过表达OPA1能够改善小鼠抑郁样行为、海马神经元凋亡及线粒体功能,OPA1可能是抑郁症的生物学标志物,成为潜在治疗靶点。Objective To investigate the effects of optic atrophy protein-1(OPA1)overexpression on hippocampal neuron apoptosis and mitochondrial function in depressed mice.Methods Thirty-two C57BL/6J mice were randomly divided into control group(CON group),chronic stress group(CMS group),chronic stress+empty vector group(CMS+NC group),chronic stress+OPA1 overexpressed vector group(CMS+OPA1 OE group).The depression model was established by chronic stress,the stress lasted for 3 weeks,and then control virus and OPA1 lentvirus overexpression were injected into the lateral ventricles of mice in CMS+NC group and CMS+OPA1 OE group,respectively.Before and 1 week after injection,depression-like behavior was evaluated by sugar water preference test and tail suspension test,and molecular biological detection was performed after behavioral test.Results After lentvirus intervention,the percentage of sugar and water preference in CMS+OPA1 OE group was higher than that in CMS and CMS+NC groups,and the tail suspension time in CMS+OPA1 OE group was lower than that in CMS and CMS+NC groups,with statistical significance(P<0.05).The apoptosis rate of hippocampal neurons and the expression rate of Caspase-3 positive cells in CMS group and CMS+NC group were higher than those in CON group,and the apoptosis rate of hippocampal neurons and the expression rate of Caspase-3 positive cells in CMS+OPA1 OE group were lower than those in CMS group and CMS+NC group,with statistical significance(P<0.05).The expression levels of mitochondrial fusion proteins MFN1 and MFN2 in hippocampus of mice in CMS group and CMS+NC group were lower than those in CON group,and the expression levels of MFN1 and MFN2 in hippocampus of mice in CMS+OPA1 OE group were higher than those in CMS group and CMS+NC group,with statistical significance(P<0.05).The adenosine triphosphate(ATP)level of mice in the hippocampus of CMS group and CMS+NC group was lower than that of CON group,and the ATP level of CMS+OPA1 OE group was higher than that of CMS group and CMS+NC group,with stati

关 键 词：慢性应激 抑郁 视神经萎缩蛋白-1 线粒体 凋亡 

分 类 号：R749[医药卫生—神经病学与精神病学]