过表达海马LINGO-1对小鼠学习和记忆能力及海马各亚区Spinophilin+树突棘的影响  

Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin+dendritic spines in different hippocampal subregions of mice

作　　者：王舜 蒋林 何琦 杨浩 王依滢 周宇宁 梁芯 张毅 晁凤蕾 张蕾 唐勇 WANG Shun;JIANG Lin;HE Qi;YANG Hao;WANG Yiying;ZHOU Yuning;LIANG Xin;ZHANG Yi;CHAO Fenglei;ZHANG Lei;TANG Yong(Department of Histology and Embryology,College of Basic Medical Sciences,Chongqing Medical University,Chongqing,400016,China)

机构地区：[1]重庆医科大学基础医学院组织学与胚胎学教研室,重庆400016

出　　处：《陆军军医大学学报》2024年第2期118-127,共10页Journal of Army Medical University

基　　金：国家自然科学基金面上项目(82002227);重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0105,cstc2020jcyj-msxmX0354)。

摘　　要：目的 脑立体定位注射腺相关病毒特异性过表达海马LINGO-1,探讨其对小鼠空间学习和记忆能力以及海马各亚区体积和Spinophilin+树突棘的影响。方法 将7月龄雄性C57小鼠按照简单随机法分为对照组和LINGO-1过表达组,对照组小鼠海马立体定位注射携带绿色荧光的空载腺相关病毒(adeno-associated virus, AAV),LINGO-1过表达组小鼠海马立体定位注射同时携带绿色荧光和LINGO-1过表达载体的AAV。运用Morris水迷宫评估小鼠的空间学习和记忆能力,荧光定量PCR及免疫荧光染色方法分别检测小鼠海马内LINGO-1基因表达水平和各亚区荧光强度,体视学三维定量小鼠海马各亚区体积及Spinophilin+树突棘总数。结果 对照组和LINGO-1过表达组病毒注射前后体质量差异无统计学意义;LINGO-1过表达诱导小鼠海马LINGO-1的mRNA水平升高、荧光强度增强(P<0.01);与对照组相比,LINGO-1过表达组小鼠在Morris水迷宫实验中的表现明显更差(P<0.05);LINGO-1过表达诱导小鼠海马各亚区体积显著下降(P<0.05,P<0.01),Spinophilin+树突棘密度显著降低(P<0.01,P<0.05),Spinophilin+树突棘数量显著减少(P<0.05)。结论 海马立体定位注射过表达LINGO-1腺相关病毒能够特异性上调小鼠海马内LINGO-1水平,海马LINGO-1的异常高表达可导致小鼠海马体积减小及Spinophilin+树突棘突触丢失,并在一定程度上损伤其空间学习与记忆能力。Objective To investigate the effects of adenovirus-associated virus(AAV)-mediated overexpression of LINGO-1 in the hippocampus on spatial learning and memory abilities,as well as the volume and Spinophilin+dendritic spines of different subregions within the hippocampus in mice.Methods Male C57 mice at 7 months of age were randomly divided into a control group and a LINGO-1 overexpression group.The control group received hippocampal stereotaxic injection of AAV carrying green fluorescent protein(GFP),while the LINGO-1 overexpression group received hippocampal stereotaxic injection of AAV carrying both GFP and LINGO-1 overexpression vector.Morris water maze was used to evaluate spatial learning and memory abilities of the mice.Quantitative PCR and immunofluorescence staining were used to detect LINGO-1 mRNA expression and fluorescence intensity in the hippocampus,and 3-dimensional stereology was used to quantify the volume and the total number of Spinophilin+dendritic spines.Results There was no significant difference in body weight between the control group and the LINGO-1 overexpression group before and after virus injection.LINGO-1 overexpression induced an increase in hippocampal LINGO-1 at mRNA level and in fluorescent intensity(P<0.01).The LINGO-1 overexpression group performed significantly worse in the Morris water maze test compared to the control group(P<0.05).Moreover,LINGO-1 overexpression led to a significant reduction in the volumes of different hippocampal subregions(P<0.05,P<0.01),accompanied by marked decreases in the density(P<0.01,P<0.05)and total number of Spinophilin+dendritic spines(P<0.05).Conclusion Stereotaxic injection of AAV-mediated LINGO-1 overexpression specifically upregulates LINGO-1 in the hippocampus of mice.Abnormally high expression of LINGO-1 in the hippocampus leads to decreased hippocampal volume and loss of Spinophilin+dendritic spines,as well as impaires spatial learning and memory abilities of mice to a certain extent.

关 键 词：LINGO-1 树突棘 突触 海马 学习 记忆 

分 类 号：R338.26[医药卫生—人体生理学] R338.64[医药卫生—基础医学] R394.3