Wang Yan-Li, Liu Li-Xia, Wang Shao-Hu, Qi Wen-Xiu
Basic Medical College, Shanxi Medical University, Taiyuan 030001, China.
Department of Physiology, Fenyang College of Shanxi Medical University, Fenyang 032200, China.
Sheng Li Xue Bao. 2016 Dec 25;68(6):775-782.
The present study was to explore the temporal and spatial distributions and variations of α7 nicotinic acetylcholine receptor (α7nAChR) and neuronal nitric oxide synthetase (nNOS) in cerebral cortex and hippocampus of Aβ-induced cognitive dysfunction rats. Sixty Sprague-Dawley (SD) rats were randomly divided into six groups. Three experimental groups were intracerebroventricularly (i.c.v.) injected with condensed-amyloid beta peptides 1-42 (Aβ, 2.5 µg/µL, 4 µL) and were observed on day 7 (7 d Aβ group), day 14 (14 d Aβ group) and day 21 (21 d Aβ group), respectively. Three control groups were i.c.v. injected with equivalent volume of normal saline and observed at the same time points as the experimental groups. The learning and memory abilities of rats were tested with Y-maze; the locations and protein expression levels of α7nAChR and nNOS in cerebral cortex and hippocampal CA1, CA3, DG regions were measured by immunohistochemistry and Western blot, respectively. The result showed that, compared with the control groups, the three experimental groups exhibited decreased learning and memory behavioral abilities, and down-regulated expressions of nNOS and α7nAChR in prefrontal cortex and hippocampal regions, especially in superficial layer of prefrontal cortex and hippocampal CA3 region. Comparisons among the three experimental groups showed that the inhibitory effects of Aβ on the abilities of learning and memory and the expressions of α7nAChR and nNOS in prefrontal cortex and hippocampus were time dependent. The results suggest that the coincident declines of α7nAChR and nNOS in prefrontal cortex and hippocampus may be the foundations of the cognitive dysfunction.
本研究旨在探讨α7烟碱型乙酰胆碱受体(α7nAChR)和神经元型一氧化氮合酶(nNOS)在Aβ诱导的认知功能障碍大鼠大脑皮质和海马中的时空分布及变化。60只Sprague-Dawley(SD)大鼠随机分为6组。3个实验组经脑室内(i.c.v.)注射凝聚态淀粉样β肽1-42(Aβ,2.5µg/µL,4µL),分别于第7天(7d Aβ组)、第14天(14d Aβ组)和第21天(21d Aβ组)进行观察。3个对照组经i.c.v.注射等量生理盐水,并在与实验组相同的时间点进行观察。用Y迷宫测试大鼠的学习和记忆能力;分别采用免疫组织化学和蛋白质免疫印迹法检测大脑皮质及海马CA1、CA3、齿状回(DG)区α7nAChR和nNOS的定位及蛋白表达水平。结果显示,与对照组相比,3个实验组的学习和记忆行为能力下降,前额叶皮质和海马区nNOS和α7nAChR的表达下调,尤其是前额叶皮质浅层和海马CA3区。3个实验组之间的比较表明,Aβ对前额叶皮质和海马的学习和记忆能力以及α7nAChR和nNOS表达的抑制作用具有时间依赖性。结果提示,前额叶皮质和海马中α7nAChR和nNOS的同时下降可能是认知功能障碍的基础。