焦虑预处理加重MPTP诱导的急性PD小鼠运动行为损害  

Anxiety preconditioning exacerbates motor behavior impairment in mice withMPTP-induced acute Parkinson′s disease

作　　者：苑晓阳 顾平[1] 刘俊骞 仇福成[1] 李冬[1] 吕俊丽 YUAN Xiao-yang;GU Ping;LIU Jun-qian;QIU Fu-cheng;LI Dong;LYU Jun-li(Department of Neurology,the First Hospital of Hebei Medical University,Shijiazhuang 050031,China;Department of Neurology,Handan Central Hospital,Hebei Province,Handan 056000,China)

机构地区：[1]河北医科大学第一医院神经内科,河北石家庄050031 [2]河北省邯郸市中心医院神经内科,河北邯郸056000

出　　处：《河北医科大学学报》2024年第3期313-320,F0003,共9页Journal of Hebei Medical University

基　　金：河北省自然科学基金面上项目(H2015206495);河北省卫健委重点科技研究计划(20200122);河北省青年自然科学基金项目(H2020206163)。

摘　　要：目的探讨焦虑预处理对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropridine,MPTP)诱导的急性帕金森病(Parkinson disease,PD)模型小鼠运动、情绪和认知的影响。方法将68只13周龄雄性C57BL/6J小鼠随机分为对照组、焦虑预处理组、急性PD模型组、焦虑预处理的急性PD模型组,每组17只,通过旷场实验,高架十字迷宫实验,爬杆试验和水迷宫实验以及黑质-纹状体酪氨酸羟化酶阳性(tyrosine hydroxylase positive,TH+)神经元的变化,探究焦虑预处理对PD小鼠运动、情绪、认知及多巴胺神经元的影响。结果焦虑预处理后第2天高架十字迷宫实验显示,焦虑预处理组开臂进入次数占总进臂次数百分比(percentage entries of open arm entries,OE%)和开臂滞留时间占总进臂时间百分比(percentage time spent on open arms,OT%)少于对照组,急性PD模型组OE%和OT%少于焦虑预处理的急性PD模型组(P<0.05)。焦虑预处理后第6天高架十字迷宫实验显示,4组的OE%和OT%比较差异均无统计学意义(P>0.05)。焦虑预处理后第5天行旷场实验,4组在中心路程百分比、时间百分比、穿格次数百分比比较差异均无统计学意义(P>0.05)。焦虑预处理后第7天爬杆实验显示,与对照组、焦虑预处理组和急性PD模型组比较,焦虑预处理的急性PD模型组爬杆时间增加(P<0.05)。焦虑预处理后第8~13天水迷宫实验显示,与对照组和焦虑预处理组比较,焦虑预处理的急性PD模型组的小鼠的寻台潜伏期较长,目标平台象限的滞留时间短,运动路程较长,穿越平台次数较长(P<0.05)。急性PD模型组和焦虑预处理的急性PD模型组黑质TH+神经元数少于对照组和焦虑预处理组,差异有统计学意义(P<0.05)。焦虑预处理的急性PD模型组黑质TH+神经元数与急性PD模型组比较差异无统计学意义(P>0.05)。急性PD模型组的纹状体TH+神经元的平均光密度值(mean optical density,MOD)值低于对照组,焦Objective To investigate the impact of anxiety preconditioning on movement,emotion and cognition in an1-methyl-4-phenyl-1,2,3,6-tetrahydropridine(MPTP)-induced Parkinson′s disease(PD)mice model.Methods Sixty-eight healthy male C57BL/6J mice(aged 13 weeks)were randomly divided into 4 groups:control group(n=17),anxiety preconditioning group(n=17),acute PD model group(n=17),and acute PD model with anxiety preconditioning group(n=17).Based on open field test,elevated plus maze test,pole climbing test,water maze test and changes of tyrosine hydroxylase positive(TH+)neurons in the nigra-striatum,the effects of anxiety preconditioning on motor,emotion and cognition and dopaminergic neurons of PD mice were investigated.Results On the 2nd day after anxiety preconditioning,the elevated plus maze test showed that the percentage of open arm entries(OE%)and open arm retention time(OT%)in the anxiety preconditioning group were lower than those in the control group.The OE%and OT%in the acute PD model group were lower than those in the acute PD model with anxiety preconditioning group(P<0.05).On the 6th day after anxiety preconditioning,the elevated plus maze test showed no statistically significant difference in OE%and OT%among the four groups(P>0.05).On the 5th day after anxiety preconditioning,an open field test was conducted,and there was no significant difference in the percentage of center distance,time,and number of grid crossings among the four groups(P>0.05).On the 7th day after anxiety preconditioning,the pole climbing test showed that compared with the control group,anxiety preconditioning group,and acute PD model group,the pole climbing time of the acute PD model with anxiety preconditioning group increased(P<0.05).On the 8th to 13th day after anxiety preconditioning,the water maze test showed that compared with the control group and anxiety preconditioning group,the mice in the acute PD model with anxiety preconditioning group had a longer latency for seeking the platform,a shorter retention time in the target pla

关 键 词：帕金森病 焦虑预处理 运动功能 认知功能 

分 类 号：R742.5[医药卫生—神经病学与精神病学]