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饮食中胆碱改变后大鼠脑烟碱受体可塑性的放射自显影分析

An autoradiographic analysis of rat brain nicotinic receptor plasticity following dietary choline modification.

作者信息

Guseva M V, Hopkins D M, Pauly J R

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington KY 40536-0082, USA.

出版信息

Pharmacol Biochem Behav. 2006 May;84(1):26-34. doi: 10.1016/j.pbb.2006.04.002. Epub 2006 Jun 6.

Abstract

Choline is known to be involved with numerous physiological functions of the nervous system and also acts as a direct acting agonist of alpha7 nicotinic acetylcholine receptors (nAChRs). The purpose of this study was to conduct a brain region-specific evaluation of changes in nAChR subtype expression following dietary choline modification. In addition, we assessed changes in body weight, food/water intake, as well as changes in spatial learning (Morris Water Maze) in response to dietary choline modification. Male Sprague-Dawley rats were exposed to standard, choline supplemented or choline deficient diets for periods of 14 or 28 days. Choline supplemented animals gained significantly less weight over the course of the experiment, in spite of the fact that there were minimal differences in food consumption between the dietary regimens. Spatial memory did not differ between animals maintained on a standard rat diet, and the choline supplemented food. Brains of the animals kept on the diets for 14 and 28 days were used for quantitative autoradiographic analysis of nicotinic receptor subtypes using 125I-Bungarotoxin (alpha7) and 125I-Epibatidine (non-alpha7). There were no significant differences in nicotinic receptor binding or physiologic parameters measured between animals fed standard and choline deficient diets. However 2 weeks of dietary choline supplementation caused significant up-regulation of alpha7 receptors without significant effect on the density of non-alpha7 nAChRs. Increases in BTX binding predominantly occurred in cortical and hippocampal brain regions and ranged between 14 and 30% depending on the brain region. The results of our study suggest that choline acts as a selective agonist at alpha7 nicotinic cholinergic receptors in the rat central nervous system.

摘要

已知胆碱参与神经系统的多种生理功能,并且还作为α7烟碱型乙酰胆碱受体(nAChRs)的直接作用激动剂。本研究的目的是对饮食中胆碱改变后nAChR亚型表达的变化进行脑区特异性评估。此外,我们评估了体重、食物/水摄入量的变化,以及对饮食中胆碱改变的空间学习(莫里斯水迷宫)变化。雄性Sprague-Dawley大鼠分别接受标准饮食、补充胆碱饮食或缺乏胆碱饮食14天或28天。尽管不同饮食方案之间的食物消耗量差异极小,但补充胆碱的动物在实验过程中体重增加明显较少。维持标准大鼠饮食的动物与补充胆碱食物的动物之间的空间记忆没有差异。将饮食14天和28天的动物大脑用于使用125I-银环蛇毒素(α7)和125I-埃博霉素(非α7)对烟碱受体亚型进行定量放射自显影分析。在喂食标准饮食和缺乏胆碱饮食的动物之间,所测量的烟碱受体结合或生理参数没有显著差异。然而,2周的饮食胆碱补充导致α7受体显著上调,而对非α7 nAChRs的密度没有显著影响。BTX结合的增加主要发生在大脑皮质和海马脑区,根据脑区不同,增加幅度在14%至30%之间。我们的研究结果表明,胆碱在大鼠中枢神经系统中作为α7烟碱胆碱能受体的选择性激动剂发挥作用。

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本文引用的文献

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