慢性应激致老年雌小鼠学习记忆损伤  

Learning and memory impairment of aged female mice induced by chronic stress

作　　者：徐家雯 屠心茹 刘锐 江瑞 陶龙 姚余有 XU Jiawen;TU Xinru;LIU Rui;JIANG Rui;TAO Long;YAO Yuyou(Department of Health Inspection and Quarantine,School of Public Health,Anhui Medical University,Hefei 230031;Anhui Provincial Key Laboratory of Population Health and Eugenics,Anhui Medical University,Hefei 230031,China)

机构地区：[1]安徽医科大学公共卫生学院卫生检验与检疫学系,安徽合肥230031 [2]安徽医科大学人口健康与优生安徽省重点实验室,安徽合肥230031

出　　处：《基础医学与临床》2023年第2期225-232,共8页Basic and Clinical Medicine

基　　金：国家自然科学基金(81773452)。

摘　　要：目的研究慢性应激致老年雌小鼠学习记忆损伤的机制。方法将20月龄ICR小鼠随机分为对照雌性组、对照雄性组、应激雌性组、应激雄性组,应激组施加为期30 d的慢性应激。用新物体识别实验和Morris水迷宫实验测定学习记忆能力。尼氏染色观察海马神经元受损,高尔基染色观察海马神经元树突,Western blot测定海马组织哺乳动物雷帕霉素靶蛋白(mTOR)、p-mTOR蛋白的表达,用ELISA测定血清促肾上腺皮质激素释放激素(CRH)水平。结果慢性应激后,仅应激雌性组有明显的学习记忆能力下降。Morris水迷宫实验中,在进行为期6 d的游泳训练后,对照雌性组、对照雄性组、应激雄性组的逃避潜伏期均有下降趋势(P<0.001,P<0.001,P<0.05),但应激雌性组下降不明显;各组游泳速度差异一致,但应激雌性组的穿越平台次数和穿越目标象限次数均显著少于对照雌性组和应激雄性组(P<0.001)。应激雌性组小鼠海马CA3、CA1、DG区神经元有显著性损伤。应激雌性组小鼠海马m-TOR、p-mTOR蛋白表达显著下降(P<0.05)。此外,慢性应激可致老年雌鼠血清CRH水平显著升高(P<0.05)。结论慢性应激可导致老年雌鼠学习记忆能力下降和海马病理改变,但对老年雄鼠作用不明显。其作用机制可能与慢性应激升高CRH,抑制老年雌鼠海马m-TOR信号通路有关。Objective To study the mechanism of learning and memory impairment in aged female mice caused by chronic stress.Methods Twenty-month-old ICR mice were randomly divided into four groups:control females,control males,stressed females,and stressed males.Chronic stress was applied to the stress group for 30 days.The learning and memory ability was measured by novel object recognition test and Morris water maze test.Damage to hippocampal neurons was observed with Nissl staining,and dendrites of hippocampal neurons were observed with Golgi-Cox staining microscopy,the expression of the mammalian target of rapamycin(mTOR)and p-mTOR in hippocampal tissue was measured by Western blot,and the level of serum corticotropin-releasing hormone(CRH)was measured by ELISA.Results There was a significant decrease in the learning and memory ability only in the stressed female group after applied stress.In the Morris water maze,after a 6-day swimming training,the escape latency decreased in the control female group,the control male group and in the stressed male group(P<0.001,P<0.001,P<0.05),but not in the stressed female group.The swimming speed was consistent across groups,but the number of platform crossings and the number of target quadrant crossings were significantly lower in the stressed female group than those in the control female and stressed male groups(P<0.001).There was significant damage to neurons in the hippocampal CA3,CA1,and DG regions of mice in the stressed female group.The expression of hippocampal m-TOR and p-mTOR protein was significantly decreased in the stressed female group of mice(P<0.05).In addition,chronic stress caused a significant increase in serum CRH levels in aged female mice(P<0.05).Conclusions Chronic stress caused learning and memory impairment and pathological damage of the hippocampus in aged female mice,but not in aged male mice,which may be related to a fact that chronic stress elevates CRH and inhibits the hippocampal m-TOR signaling pathway in aged female mice.

关 键 词：慢性应激 记忆损伤 m-TOR P-MTOR CRH 

分 类 号：R749.16[医药卫生—神经病学与精神病学]