Exercise-induced neuronal effects and the 5-HT3 receptor

Abstract

Fourteen subtypes of the serotonin (5-hydroxytryptamine, 5-HT) receptor have been delineated, and these subtypes are assigned to seven 5-HT receptor subfamilies (5-HT1-7). Among the 5-HT receptor subfamilies, the 5-HT type 3 (5-HT3) receptor is the only ionotropic receptor. Previous studies have reported abundant expression of the 5-HT3 receptor in the hippocampus, and the involvement in the mood and memory. However, possible roles of the 5-HT3 receptor in hippocampal neurogenesis remains unknown. We performed immunohistochemical analyses of adult hippocampal neurogenesis in the 5-HT3A receptor-deficient mice (htr3a-/-mice). We found that basal cell proliferation and neurogenesis in the hippocampal dentate gyrus of htr3a-/-mice were normal. Exercise is known to increase hippocampal neurogenesis, cause antidepressant effects and enhance learning ability. Immunohistochemical and behavioral analyses of htr3a-/-mice revealed that a lack of the 5-HT3 receptor led to a blockade of the exercise-induced neurogenesis in the hippocampus and antidepressant effects, but not of enhanced learning ability. Moreover, we have shown that the 5-HT3 receptor agonist enhanced cell proliferation in the hippocampal dentate gyrus. Our results indicate that the 5-HT3 receptor is indispensable for increased hippocampal neurogenesis and antidepressant effects induced by exercise. Amongst the serotonin (5-hydroxytryptamine, 5-HT) receptor subfamilies [1] , the 5-HT3 receptor is the only ligand-gated ionotropic receptor [2,3] . Previous studies have shown that the 5-HT3 receptor is expressed in the limbic brain regions, such as hippocampus, amygdala and prefrontal cortex [4,5,6,] . Furthermore, many reports have indicated the involvement of the 5-HT3 receptor in emotional and cognitive functions, such as mood and memory [1,7,8,9,10,11] . The dentate gyrus of the hippocampus is a brain region where adult neurogenesis prominently occurs. As for the hippocampus, despite enriched expression of the 5-HT3 receptor, its possible roles in adult hippocampal neurogenesis remains uncertain. KeywordsIt is well known that exercise causes a variety of influences on brain structure and function [12,13] . The hippocampus is one of the brain regions affected by exercise stimulation. Actually, previous studies have shown that exercise induced increase in adult neurogenesis [14,15] and synaptogenesis [16,17] in the hippocampus at the morphological levels. The hippocampus is involved in the cognitive and emotional processes, and the altered function of the hippocampus has influences on animal behavior. Exercise has been reported to cause antidepressant effects [18,19,20,21,22] and learning enhancement [15,23,24] in human and rodents, and it is suggested that the hippocampus is implicated in these behavioral changes. Importantly, Neurotransmitter 2015; 2: e764. doi: 10.14800/nt. 764; © 2015 by Makoto Kondo, et al. http://www.smartscitech.com/index.php/nt Page 2 of 5 serotonin is thought to be one of the most important molecules that mediate these benefi...