Sex-dependent and independent effects of long-term voluntary wheel running on Bdnf mRNA and protein expression

Abstract

The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited. PurposeTo examine the effect of five months of voluntary wheel running on hippocampal mRNA and protein expression of factors critical for exercise-induced structural and functional plasticity in male and female adult mice. MethodsAt 8weeks of age, male and female C57BL/6 mice were individually housed with (PA; n=20; 10 male) or without (SED; n=20; 10 male) access to a computer monitored voluntary running wheel. At 28weeks, all mice were sacrificed and hippocampi removed. Total RNA was isolated from the hippocampus and expression of total Bdnf, Bdnf transcript IV, tPA, Pgc-1a, GluR1, NR2A, and NR2B were assessed with quantitative RT-PCR and total and mature Bdnf protein were assessed with ELISA. ResultsWe found significantly higher Bdnf IV mRNA expression in PA males (p=0.03) and females (p=0.03) compared to SED animals. Total Bdnf mRNA expression was significantly greater in PA males compared to SED males (p=0.01), but there was no difference in females. Similarly, we observed significantly higher mature Bdnf protein in PA males compared to SED males (p=0.04), but not in females. ConclusionThese findings indicate that the impact of long-term voluntary wheel running on transcriptional and post-translational regulation of Bdnf may be sex-dependent, though the activity-dependent Bdnf IV transcript is sensitive to exercise independent of sex.