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

Abstract

Choline is known to be involved with numerous physiological functions of the nervous system and also acts as a direct acting agonist of α7 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 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 125 I-Bungarotoxin (α7) and 125 I-Epibatidine (non-α7). 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 α7 receptors without significant effect on the density of non-α7 nAChRs. Increases in BTX binding predominantly occurred in cortical and hippocampal brain regions and ranged between 14 and 30 percent depending on the brain region. The results of our study suggest that choline acts as a selective agonist at α7 nicotinic cholinergic receptors in the rat central nervous system.

Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline

“…Increases in the number of α7 receptors could have increased the release of GABA, thus increasing inhibition of pyramidal cell firing in response to the second stimulus. Increases in α-bungarotoxin binding have been observed with subchronic (2 weeks; Guseva et al 2006) or chronic dietary choline supplementation in adult rats (Coutcher et al 1992).…”

Dietary Choline Supplementation Improves Behavioral, Histological, and Neurochemical Outcomes in a Rat Model of Traumatic Brain Injury

“…Cholineevoked electrophysiological responses from single cells or hippocamlpal slices are blocked by either methyllycaconitine or ␣ bungarotoxin (BTX), selective ␣7 antagonists (Alkondon et al, 1997;Albuquerque et al, 1998;Fayuk and Yakel, 2004). Dietary supplementation with choline results in selective increases the density of ␣7 nicotinic receptors in multiple brain regions, consistent with the actions of a nicotinic cholinergic agonist (Morley et al, 1977;Coutcher et al, 1992;Guseva et al, 2006).…”

Prenatal choline supplementation increases sensitivity to time by reducing non-scalar sources of variance in adult temporal processing

“…Previous research has shown that adult rats treated prenatally with supplemental choline, a selective agonist of α7 nicotinic acetylcholine receptors (α7-nAChR - Alkondon et al, 1997Alkondon et al, , 1999Guseva et al, 2006), exhibit enhanced attention and precision in the temporal control of responding when trained in a peak-interval (PI) timing procedure (Meck and Williams 1997a, b). This enhancement can be related to an increase in rats' sensitivity to the inhibitory effects of a signaled delay to reinforcement and the associated resetting of an internal clock by the delivery of reinforcement (Matell and Meck 1999;Cheng et al 2006).…”