摘要
目的研究单次腹腔注射肿瘤坏死因子α(TNF-α)对小鼠认知功能及焦虑情绪的影响及可能的作用途径。方法根据自主活动性和体质量将BALB/c小鼠随机分为对照组和TNF-α处理组。采用Morris水迷宫空间探索实验、高架十字迷宫实验、在体电生理实验,分别观察TNF-α0.1、0.2和0.4 mg/kg单次腹腔注射1 h对小鼠空间记忆提取过程、焦虑样行为、突触可塑性的影响;采用Morris水迷宫定向航行实验,观察在学习训练的第1、3、5天训练前1 h腹腔注射TNF-α0.2 mg/kg对小鼠空间记忆获取与巩固功能的影响;采用尼氏染色实验,观察单次腹腔注射TNF-α0.2 mg/kg 1 h对小鼠不同脑区神经元尼氏体数目的影响。结果Morris水迷宫实验中,定向航行实验阶段给予TNF-α后小鼠逃避潜伏期和穿环次数无明显变化,提示定向航行阶段给予TNF-α对小鼠空间学习记忆能力无明显损害。空间探索实验前1 h腹腔注射TNF-α0.1和0.4 mg/kg后小鼠逃避潜伏期明显延长(均P<0.05),给予TNF-α0.2和0.4 mg/kg 1 h后小鼠穿环次数明显减少(P<0.05,P<0.01),提示空间探索阶段单次腹腔注射TNF-α可致小鼠空间记忆提取功能明显受损;高架十字迷宫实验中,与对照组相比,单次腹腔注射TNF-α0.2 mg/kg 1 h后测试发现小鼠进入开放臂时间以及在开放臂时间占在开闭臂总时间百分比显著降低(P<0.01),给予TNF-α0.4 mg/kg后小鼠在开放臂时间占在开闭臂总时间百分比显著降低(P<0.01),提示小鼠出现焦虑样行为;在体电生理实验和组织病理学实验结果表明,与对照组相比,单次腹腔注射TNF-α0.2和0.4 mg/kg 1 h后小鼠平均群峰电位明显降低(P<0.05,P<0.01),给予TNF-α0.2 mg/kg 1 h后小鼠海马神经元尼氏体数量明显减少(P<0.01),提示小鼠长时程增强(LTP)及海马神经元明显受损。结论TNF-α的急性升高可致小鼠空间学习记忆功能障碍并表现出焦虑样行为,可能与TNF-α对海马LTP及神经元的�
Objective To investigate the effects of a single intraperitoneal injection of tumor necrosis factor-α(TNF-α)on the cognitive function and anxiety in mice.Methods BALB/c mice were randomly divided into the control group and TNF-αtreated groups according to their autonomous activities and body mass.A single dose of TNF-α at 0.1,0.2,or 0.4 mg/kg was injected into the peritoneal cavity.After 1 hour of the injection,the retrieval process of spatial memory,anxiety-like behavior,and synaptic plasticity were evaluated by Morris water maze spatial probe experiment,elevated plus maze,and in vivo electrophysiological recording,respectively.Meanwhile,mice were i.p.0.2 mg/kg TNF-α1 hour before training on 1st,3rd,and 5th days.The effects of TNF-α on spatial memory acquisition and consolidation were assessed with the Morris water maze place navigation experiment.The number of Nissl bodies in different brain regions was calculated with the Nissl staining 1 hour after the TNF-αinjection at 0.2 mg/kg.Results In the Morris water maze experiment,there was no significant change in the escape latency and the number of crossing the plateform of the mice after TNF-α was given during the place navigation experiment,indicating that there was no significant damage to spatial learning and memory ability of mice after TNF-αadministered in the place navigation stage.The escape latency of mice was significantly prolonged after intraperitoneal injection of TNF-α at 0.1 and 0.4 mg/kg 1 hour before the space exploration experiment(both P<0.05)and the number of crossing the plateform of mice was significantly reduced after TNF-α injection at 0.2 and 0.4 mg/kg(P<0.05,P<0.01),suggesting that the spatial memory extraction function of mice was significantly impaired after the single intraperitoneal injection of TNF-αduring the spatial probe stage.In the elevated plus maze experiment,compared with the control group,the time in the open arm and the time in the open arms as a percentage of the total time in the open and close arm of mice dec
作者
郭彦飞
肖智勇
王陈
黄晏
周文霞
张永祥
GUO Yan-fei;XIAO Zhi-yong;WANG Chen;HUANG Yan;ZHOU Wen-xia;ZHANG Yong-xiang(Nanjing University of Chinese Medicine,Nanjing 210023,China;State Key Laboratory of Toxicology and Medical Countermeasure,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)
出处
《国际药学研究杂志》
CAS
北大核心
2020年第10期834-841,共8页
Journal of International Pharmaceutical Research
