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

发布时间：2018-06-25 11:47

本文选题：雌二醇 + 神经元性一氧化氮合酶　；参考：《南京医科大学学报(自然科学版)》2015年07期

【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(n NOS)m RNA和蛋白表达水平,并标记海马齿状回n NOS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n NOS m RNA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n NOS m RNA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n NOS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。
[Abstract]:Aim: to investigate the effect and mechanism of estradiol (E 2) on cognitive dysfunction in ovariectomized OVX rats induced by chronic mild stress (chronic mild stress. Methods: the animal model of depression was established by CMS, and the plasma corticosterone levels were measured in normal and depressed mice. Two weeks later, OVX mice were given E2 and continued to model for 1 week. Morris water maze was used to test the spatial learning and memory ability after the last administration. The levels of plasma E2 and the expression of neuronal nitric oxide synthase (nNOS) mRNA and protein in hippocampus were detected and the number of nNOS positive cells in dentate gyrus was labeled. Hippocampal neurons of female fetal rats were cultured in vitro. The expression of nNOS mRNA and protein were detected 24 hours after cortisone (Cort) and Cort combined with E2. In addition, extracellular regulated kinase (ERK) phosphorylation was detected 24 hours after E 2 administration in vitro. Results the levels of plasma corticosterone in mice were significantly increased after the establishment of CMS. Exogenous E2 supplementation could reverse the decrease of plasma E2 level in OVX female rats induced by CMS and decrease the expression of nNOS mRNA and protein in hippocampus induced by Cort in vitro, and restore the spatial learning and memory function of OVX female rats. In addition, E 2 significantly increased ERK phosphorylation in hippocampal neurons of female fetal rats. Conclusion the abnormal expression of nNOS in hippocampus of female rats with OVX depression induced by CMS was reversed and the spatial learning and memory deficit was improved. The effect may be mediated by ERK phosphorylation.
【作者单位】：南京医科大学药学院药理学与药物化学系;南京医科大学药学院干细胞与神经再生研究所;
【基金】：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)
【分类号】：R965

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