Maternal exercise during pregnancy mitigates behavioral and morphological deficits induced by early-life stress

Maternal separation (MS) is a widely used model of early-life stress that induces long-lasting behavioral and neurobiological alterations in offspring. Maternal exercise during pregnancy has been proposed as a non-pharmacological strategy to counteract these adverse effects. Pregnant Wistar rats were assigned to either a sedentary or exercise group, with the exercise group having free access to a running wheel throughout pregnancy. Offspring were divided into four experimental groups: offspring of sedentary mothers without MS (SedMS-), offspring of sedentary mothers with MS (SedMS+), offspring of exercised mothers without MS (ExMS-), and offspring of exercised mothers with MS (ExMS+). Behavioral assessments, conducted in adulthood starting at postnatal day 90 (P90), included the open field, elevated plus maze, forced swim test, and contextual fear conditioning. Morphological analysis of the hippocampus was performed using isotropic fractionation to quantify total neuronal and non-neuronal cells. Epigenetic changes were evaluated through chromatin immunoprecipitation (ChIP) using anti-acetylated histone H3 and H4, followed by amplification of bdnf exons IV and VI. Maternal separation increased depressive-like behavior and impaired hippocampus-dependent memory, effects that were attenuated by maternal exercise. MS also elevated non-neuronal cell numbers and reduced neuronal cells in the hippocampus, whereas prenatal exercise reversed these alterations. No significant group differences were found in histone acetylation at the Bdnf loci examined. Maternal exercise during pregnancy mitigates behavioral and morphological deficits induced by early-life stress, supporting its neuroprotective role in preserving hippocampal integrity and function. Although no significant epigenetic changes were detected, these findings suggest that maternal physical activity may be a promising intervention to mitigate the long-term neurobiological consequences of early-life adversity.