文章摘要
刘 华,胡 瑶,朱东亚.雌二醇改善慢性温和性应激诱导的去卵巢雌鼠空间学习记忆障碍[J].南京医科大学学报,2015,(7):992~998
雌二醇改善慢性温和性应激诱导的去卵巢雌鼠空间学习记忆障碍
Estradiol reverses spatial learning and memory deficit induced by chronic mild stress in female ovariectomized mice
投稿时间:2014-11-06  
DOI:10.7655/NYDXBNS20150717
中文关键词: 雌二醇  神经元性一氧化氮合酶  胞外调节激酶  空间学习记忆
英文关键词: E2  nNOS  ERK  spatial learning and memory
基金项目:国家自然科学基金青年项目(81301162);国家自然科学基金重点研究计划(91232304)
作者单位
刘 华 南京医科大学药学院药理学与药物化学系,江苏 南京 211100 
胡 瑶 南京医科大学干细胞与神经再生研究所,江苏 南京 211100 
朱东亚 南京医科大学药学院药理学与药物化学系,江苏 南京 211100南京医科大学干细胞与神经再生研究所,江苏 南京 211100 
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中文摘要:
      目的:探讨雌二醇(E2)对慢性温和性应激(chronic mild stress,CMS)引起的卵巢摘除(ovariectomized,OVX)抑郁模型雌鼠认知功能障碍的改善作用及其机制?方法:采用CMS制备抑郁症动物模型,检测正常及抑郁症模型小鼠的血浆皮质酮水平?造模2周后开始给予OVX小鼠E2,同时继续造模1周?末次给药后采用Morris水迷宫测试其空间学习记忆能力?检测血浆E2以及海马神经元型一氧化氮合酶(nNOS) mRNA和蛋白表达水平,并标记海马齿状回nNOS阳性细胞数?体外采用雌性胎鼠海马神经元原代培养,给予皮质酮(CORT)及CORT合并E2后24 h,检测nNOS mRNA及蛋白表达水平?此外,体外给予E2后24 h,检测胞外调节激酶(ERK)磷酸化水平?结果:CMS造模后小鼠血浆皮质酮水平均显著上升?外源性补充E2可逆转CMS诱导的OVX雌鼠血浆E2水平的降低?CMS及体外CORT诱导的海马nNOS mRNA及蛋白表达水平的降低,并恢复OVX雌鼠空间学习记忆功能?此外,E2可显著升高雌性胎鼠海马神经元的ERK磷酸化水平?结论:E2逆转了由CMS诱导的OVX抑郁模型雌鼠海马nNOS的异常表达,并改善了其空间学习记忆缺陷,其作用可能是通过ERK磷酸化介导的?
英文摘要:
      Objective:To explore the effects and mechanisms of E2 on cognitive disorder induced by chronic mild stress (CMS) of depressive female ovariectomized (OVX) mice. Methods:We used CMS as the animal model for stress-induced depression,and detected plasma corticosterone of normal and depressive mice. Then,we examined whether 7 days treatment using E2 could ameliorate the effects of CMS on plasma E2 in female OVX mice. Morris water maze was performed to test spatial learning and memory ability of mice after last treatment. At the same time,we analyzed the mRNA and protein expression of nitric oxide synthase (nNOS) in hippocampus as well as positive nNOS neurons of dentate gyrus. Primary cultured hippocampal neurons from female embryo were adopted,the mRNA and protein expressions of nNOS were detected in neurons exposed to corticosterone (CORT) or CORT combined with E2 for 24 h. In addition,we detected the level of extracellular signal-regulated kinase (ERK) phosphorylation in neurons exposed to E2 for 24 h. Results:Plasma CORT of female and male mice was significantly increased after CMS. Ectogenic supplement of E2 reversed the decrease of plasma E2 and spatial learning and memory deficit,as well as the decrease of hippocampal nNOS mRNA and protein expression induced by CMS in female OVX mice. In vitro,E2 reversed nNOS mRNA and protein expression induced by corticosterone in primary cultured cortical hippocampal neurons from female embryo. In addition,E2 significantly up-regulated ERK phosphorylation in the hippocampal neurons from female embryo. Conclusion:E2 could reverse the spatial learning and memory deficits and abnormal hippocampal nNOS expression induced by chronic stress in female OVX mice. The hippocampal neuronal ERK phosphorylation is involved in the effects of E2.
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