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

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.