Running-induced epigenetic and gene expression changes in the adolescent brain

Abstract

Physical exercise is associated with positive neural functioning. Here we examined the gene expression consequences of 1 week of voluntary wheel running in adolescent male mice. We assayed expression levels of genes associated with synaptic plasticity, signaling pathways, and epigenetic modifying enzymes. Two regions were examined: the hippocampus, which is typically examined in exercise studies, and the cerebellum, an area directly involved in motor control and learning. After 1 week of exercise, global acetylation of histone 3 was increased in both brain regions. Interestingly this was correlated with increased brain derived neural growth factor in the hippocampus, as noted in many other studies, but only a trend was found in cerebellum. Differences and similarities between the two areas were noted for genes encoding functional proteins. In contrast, the expression pattern of DNA methyltransferases (Dnmts) and histone deacetylases (Hdacs), genes that influence DNA methylation and histone modifications in general, decreased in both regions with exercise. We hypothesize that epigenetic mechanisms, involving many of the genes assessed here, are essential for the positive affects of exercise on behavior and suspect these data have relevance for adolescent boys.

Keywords: Adolescent; BDNF; Cerebellum; Epigenetic; Exercise; Puberty.

Fig. 1

Voluntary exercise increases histone H3 acetylation in the cerebellum and hippocampus of juvenile mice. Mice were sacrificed on postnatal Day 53 after 1 week in a cage with a locked running wheel (sedentary red histograms) or with an unlocked running wheel (exercised green histograms). Levels of acetylated histone H3 were assessed by Western Blotting. Representative immunoblot from the cerebellum of a sedentary (SED) compared to exercised (EXE) mouse. For each mouse, the amount of acetylated histone H3 in the cerebellum (n = 8 per group) and hippocampus (n = 5 per group) was divided by the total amount of histone 4 in each area to normalize the amount of protein loaded across samples. Each bar represents the mean ± SEM. Significantly different from sedentary *p = 0.05, **p < 0.01. Acetyl = acetylation, H3 = histone 3, H4 = histone 4.