Impact of maternal exercise on neurodevelopment and gut microbiota in offspring from advanced-age mice.

The effects of maternal exercise on hippocampal neurogenesis, synaptic protein expression, and gut microbiome composition in the offspring of older females were investigated. Male offspring from female C57BL/6 mice were divided into four groups: offspring of young female group (CON), offspring of exercised young female group, offspring of advanced-age female group (AMA), and offspring of exercised advanced-age female group (AMA+EX). The exercised group received 8 weeks of treadmill training before and during pregnancy. Male offspring were assessed at 4 weeks of age. Hippocampal neurogenesis was assessed by 5-bromo-2'-deoxyuridine/neuronal double immunofluorescence staining. Expression of synaptic plasticity-related proteins, including brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95), was analyzed by Western blot. Gut microbiome composition and diversity were assessed using 16S rRNA sequencing of fecal samples. Offspring born to AMA females had significantly reduced hippocampal neurogenesis and lower expression levels of BDNF and PSD-95 compared to the CON group. In the AMA+EX group, maternal treadmill exercise significantly improved these deficits, restoring both neurogenesis and synaptic protein expression. In contrast, gut microbiota analysis showed that microbial richness and alpha diversity were reduced in the offspring of exercised females, despite the relatively high diversity in the CON and AMA groups, especially in the AMA+EX group. Older mothers impair hippocampal neurogenesis and synaptic protein expression in offspring, and alter gut microbial diversity. Maternal exercise may alleviate age-related neurodevelopmental disorders, but may also reduce microbial diversity in the offspring's gut.