长期丰富环境对由神经毒素MPTP所致的帕金森病小鼠模型抑郁情绪的作用  

Effect of long-term environmental enrichment on depressed mood in a mouse Parkinson’s disease model induced by neurotoxin MPTP

作　　者：车祥源 郑志勇[1] 李超堃 邢红霞 CHE Xiang-Yuan;ZHENG Zhi-Yong;LI Chao-Kun;XING Hong-Xia(Department of Neurology,The First Affiliated Hospital of Xinxiang Medical University/Henan Provincial Key Laboratory of Nerve Repair,Xinxiang,Henan 453100,China;Department of Physiology and Neurobiology,School of Basic Medicine,Xinxiang Medical University,Xinxiang,Henan 453000,China;Department of Neurology,Third Affiliated Hospital of Xinxiang Medical University,Xinxiang,Henan 453003,China)

机构地区：[1]新乡医学院第一附属医院神经内科/河南省神经修复重点实验室,河南新乡453100 [2]新乡医学院基础医学院生理学与神经生物学教研室,河南新乡453000 [3]新乡医学院第三附属医院神经内科,河南新乡453003

出　　处：《国际神经病学神经外科学杂志》2021年第3期239-243,共5页Journal of International Neurology and Neurosurgery

摘　　要：目的探讨长期丰富环境(EE)对由神经毒素MPTP所致的帕金森病(PD)小鼠模型抑郁情绪的作用。方法采用随机分组法将40只7月龄雄性C57BL/6N小鼠,分为EE+MPTP组、EE+NS组、SE+MPTP组与SE+NS组,每组10只。EE组和标准环境(SE)组在干预3个月后,MPTP组小鼠进行神经毒素MPTP造模(腹腔注射,30 mg/kg),每天注药1次,连续7 d;NS组给予腹腔注射等量的0.9%NaCl作为对照观察。采用行为学方法评估小鼠行为学表现。行免疫组织化学染色方法观察酪氨酸羟化酶(TH)与5-HT1A受体阳性面密度值变化情况。结果行为学结果显示MPTP组的小鼠的强迫游泳评分较NS组小鼠低(P<0.01);悬尾实验静止不动时间延长(P<0.01)。EE+MPTP组的上述抑郁表现轻于SE+MPTP组(P<0.05)。从免疫组织化学染色结果中发现,SE+MPTP组和EE+MPTP组小鼠的TH与5-HT_(1A)受体阳性表达水平较NS组小鼠降低(P<0.01),而EE+MPTP组小鼠TH及5-HT_(1A)受体阳性表达水平降低程度较SE+MPTP组小鼠小(P<0.05)。结论 MPTP小鼠的行为学异常以及TH阳性面密度值减少提示PD模型制作成功。EE+MTPT组小鼠5-HT_(1A)受体受损较SE+MPTP组小鼠轻,提示丰富环境可能缓解MPTP诱导的PD小鼠模型的抑郁情绪。Objective To investigate the effect of long-term environmental enrichment(EE) on depressed mood in a mouse Parkinson’s disease(PD) model induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Methods A total of 40 seven-month-old male C57 BL/6 N mice were randomly divided into EE+MPTP(n=10),EE+normal saline(NS)(n=10),standard environment(SE)+MPTP(n=10),and SE+NS(n=10) groups.After three months of intervention with EE or SE,the mice in the MPTP groups were subjected to neurotoxin MPTP(intraperitoneal injection,30 mg/kg)once daily for 7 consecutive days for modeling.The mice in the NS groups were given intraperitoneal injection of the same amount of 0.9%NaCl as the control study.Behavioral methods were used to evaluate the behavioral manifestations of mice,and immunohistochemical staining was performed to observe the positive areal density values of tyrosine hydroxylase(TH)and 5-hydroxytryptamine 1 A(5-HT1 A) receptor.Results The behavioral results showed that the mice in the MPTP groups had a significantly lower forced swimming score(P<0.01) and a significantly long erimmobility time in the tail suspension test(P<0.01) than those in the NS groups.The mice in the EE+MPTP group had significantly milder depression symptoms mentioned above than those in the SE+MPTP group(P<0.05).The results of immunohistochemical staining showed that the mice in the SE+MPTP group and EE+MPTP group had significantly lower positive expression levels of TH and 5-HT1 A receptor than those in the NS groups(P<0.01),while the mice in the EE+MPTP group had significantly smaller decreases in positive expression levels of TH and 5-HT1 A receptor than those in the SE+MPTP group(P<0.05).Conclusions The behavioral abnormalities of MPTP mice and the reduction in TH positive areal density value suggested that the PD model was successfully established.The mice in the EE+MTPT group had significantly milder 5-HT1 A receptor damage than those in the SE+MPTP group,suggesting that environmental enrichment may alleviate the depressed mo

关 键 词：帕金森病 丰富环境 1-甲基-4-苯基-1 2 3 6-四氢吡啶 行为学 5-HT_(1A)受体 抑郁情绪 小鼠 

分 类 号：R742.[医药卫生—神经病学与精神病学]