摘要
目的:探讨超氧化物歧化酶1(superoxide dismutase1,SOD1)的两种突变类型G41S和G41D对小鼠认知行为的影响。方法:构建过表达人源性SOD1WT、SOD1G41S、SOD1G41D的重组腺相关病毒(recombinant adeno-associated virus,rAAV)及不携带目的基因的空白病毒,立体定位注射到小鼠的双侧内侧前额叶皮层(medial prefrontal cortex,mPFC),根据注射病毒的不同,分为CONTROL组、SOD1WT组、SOD1G41S组及SOD1G41D组(均n=16)。1个月后,对小鼠进行旷场实验、Y迷宫自发交替实验、三箱社交实验、追踪条件恐惧实验,观察突变基因对小鼠认知行为的影响。结果:在旷场实验中,SOD1WT组[(39.67±6.04)m]的运动路程明显多于SOD1G41D组[(28.47±6.92)m,P=0.034];在Y迷宫自发交替实验中,SOD1WT组[(40.56±10.12)次,(32.63±8.19)次]及SOD1G41S组[(36.75±9.43)次,(29.06±8.32)次]的总进臂数和实际交替进臂数明显高于SOD1G41D组[(24.50±11.30)次,(18.38±9.09)次,均P<0.05];在三箱社交实验中,SOD1G41D组在含有老鼠的区域停留时间[(279.08±134.94)s]和对侧空金属笼子区域[(218.54±125.63)s]差异无统计学意义(t=1.313,P=0.199),SOD1WT组及SOD1G41S组在陌生鼠1[(253.07±55.60)s,(253.20±57.61)s]及陌生鼠2[(243.44±55.33)s,(239.76±67.49)s]所在区域停留时间差异无统计学意义(P>0.05),SOD1WT组、SOD1G41S组表现为社交趋新障碍;在追踪条件恐惧实验的测试阶段,SOD1G41S组的僵直时间百分比明显高于其他实验组和CONTROL组(P<0.05)。结论:SOD1G41S和SOD1G41D对小鼠的认知行为产生了明显的改变,相同位点上的两种突变类型产生的认知行为改变存在明显差异。
Objective:To investigate the effects of superoxide dismutase 1(SOD1)mutations G41D and G41S on the cognitive behavior of mice.Methods:The recombinant adeno-associated virus(rAAV)which overexpressed human SOD1WT,SOD1G41S,SOD1G41D and the blank virus without the target gene were constructed,then they were stereotaxic injected into mice bilateral medial prefrontal cortex(mPFC)area respectively.According to the difference of injected virus,they were divided into CONTROL group,SOD1WT group,SOD1G41S group and SOD1G41D group(n=16 in each group).One month later,open field test,Y-maze spontaneous alternation experiment,three box social interaction experiment and trace fear conditioning test were conducted to observe the effect of mutant gene on cognitive behavior of mice.Results:In the open field test,the movement distance of SOD1WT group((39.67±6.04)m)was significantly higher than that of SOD1G41D group((28.47±6.92)m,P=0.034).In the Y-maze spontaneous alternations experiment,the number of arm entries and actual alternations of arm entries of SOD1WT group((40.56±10.12)times,(32.63±8.19)times)and SOD1G41S group((36.75±9.43)times,(29.06±8.32)times)were significantly higher than those of SOD1G41D group((24.50±11.30)times,(18.38±9.09)times,P<0.05).In the three-compartment social experiment,there was no statistical difference between the residence time of SOD1G41D group in the area containing mouse((279.08±134.94)s)and the empty metal cage area((218.54±125.63)s)(t=1.313,P=0.199).SOD1WT group and SOD1G41S group showed no statistical difference in the residence time in the regions of the unfamiliar mouse 1((253.07±55.60)s,(253.20±57.61)s)and the unfamiliar mouse 2((243.44±55.33)s,(239.76±67.49)s)(P>0.05),and SOD1WT group and SOD1G41S group presented new social barrier.In the test stage of trace fear condition task,the percentage of freezing time of SOD1G41S group was significantly higher than that of other experimental groups and CONTROL group(P<0.05).Conclusion:SOD1G41S and SOD1G41D have significantly changed the cognitive behavior of mice,and the two types of mutations at the same site have significant differences in the cognitive behavior changes.
作者
任曼丽
史明超
裘冯卓
杨涛
牛琦
金庆文
Ren Manli;Shi Mingchao;Qiu Fengzhuo;Yang Tao;Niu Qi;Jin Qingwen(Department of Neurology,the Affiliated Sir Run Run Hospital of Nanjing Medical University,Nanjing 211166,China;Department of Geriatric Neurology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2020年第7期577-583,共7页
Chinese Journal of Behavioral Medicine and Brain Science
基金
国家自然科学基金项目(81671117)。
