Effects of Maternal Physical Exercise on Global DNA Methylation and Hippocampal Plasticity of Rat Male Offspring

Abstract

Intrauterine exposure to exercise is beneficial to cognition of the offspring. Although it is advisable to start practicing physical exercise during pregnancy, it is probable that practitioners or sedentary women keep their previous habits during gestation. This study was designed to evaluate the effects of maternal aerobic exercise initiated before and maintained during gestation, or performed in these isolated periods, on cognition and plasticity in the hippocampus of offspring. Groups of male pups were categorized by the exposure of their mothers to: treadmill off (sedentary, SS), pregestational exercise (ES), gestational exercise (SE) or combined protocols (EE). Between postnatal day 20 (P20) and P23 the offspring received one daily 5-bromo-2′-deoxiuridine (BrdU) injection and, from P47 to P51, were evaluated by the Morris water maze task. At P53, hippocampal global DNA methylation, survival of progenitor cells (BrdU), Brain-derived Neurotrophic Factor (BDNF) and reelin levels were measured. The offspring from ES, SE and EE mothers demonstrated improved spatial learning compared to SS, but hippocampal DNA methylation was significantly modified only in the offspring from ES mothers. The offspring from ES and SE mothers presented higher number of BrdU+ and reelin+ hippocampal cells than EE and SS. No differences were observed in the BDNF levels among the groups. The maternal pregestational and gestational isolated exercise protocols showed similar effects for offspring plasticity and spatial cognitive ability, while the combined protocol simply improved their spatial learning. Interestingly, only pregestational exercise was able to induce plasticity in the offspring hippocampus associated with modulation of global DNA methylation.