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α7nAChR和nNOS在Aβ诱导的认知障碍大鼠皮质及海马表达的时间和空间变化

王艳莉, 刘丽霞, 王少虎, 祁文秀

山西医科大学基础医学院，太原 030001；山西医科大学汾阳学院生理学教研室，汾阳 032200

摘要

本研究旨在观察α7烟碱型乙酰胆碱受体(α7 nicotinic acetylcholine receptor, α7nAChR)与神经元型一氧化氮合酶(neuronal nitric oxide synthetase, nNOS)在Aβ诱导的认知障碍大鼠皮质和海马时间和空间的分布与变化。取Sprague-Dawley (SD)大鼠60只，随机分成6组，其中3个实验组分别经侧脑室注射凝聚态Aβ1-42 (2.5 µg/µL, 4 µL)，连续观察7 d (7 d Aβ组)、14 d (14 d Aβ组)和21 d (21 d Aβ组)；3个对照组则分别注射和实验组等量生理盐水并观察相同的时间。用Y迷宫刺激器检测大鼠的学习和记忆行为能力，用免疫组织化学和Western blot检测皮质和海马CA1、CA3、DG各区α7nAChR和nNOS阳性细胞分布和蛋白表达量的变化。结果显示，与各自对照组相比，3个实验组大鼠的学习和记忆行为能力降低，前额叶皮质和海马各区α7nAChR和nNOS的表达均显著下调，特别在前额叶皮质浅层和海马CA3区变化明显；3个实验组之间比较结果显示，Aβ诱导的认知障碍大鼠学习和记忆功能、前额叶皮质和海马α7nAChR和nNOS表达均随着Aβ作用时间的延长呈进行性下降。以上结果提示，前额叶皮质和海马α7nAChR和nNOS表达的共同降低可能是Aβ诱导的大鼠认知功能障碍的基础。

关键词： 阿尔茨海默病; α7烟碱型乙酰胆碱受体; 神经元型一氧化氮合酶; 皮质; 海马; 时间和空间

分类号：R338

[Temporal and spatial changes of α7nAChR and nNOS in cerebral cortex and hippocampus of Aβ-induced cognitive dysfunction rats.] [Article in Chinese]

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

Abstract

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 (Aβ1-42, 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.

Key words: Alzheimer’s disease; α7 nicotinic acetylcholine receptor; neuronal nitric oxide synthetase; hippocampus; cortex; temporal and spatial

收稿日期：2016-03-17　　录用日期：2016-07-01

通讯作者：祁文秀　　E-mail: fycqwx@163.com

引用本文：

王艳莉, 刘丽霞, 王少虎, 祁文秀. α7nAChR和nNOS在Aβ诱导的认知障碍大鼠皮质及海马表达的时间和空间变化[J]. 生理学报 2016; 68 (6): 775-782.

WANG Yan-Li, LIU Li-Xia, WANG Shao-Hu, QI Wen-Xiu. [Temporal and spatial changes of α7nAChR and nNOS in cerebral cortex and hippocampus of Aβ-induced cognitive dysfunction rats.] [Article in Chinese]. Acta Physiol Sin 2016; 68 (6): 775-782 (in Chinese with English abstract).