Transgenerational effects of exercise on mouse brain and cognition

Lifestyle induces long lasting effects on the brain and cognition, with some interventions like stress including transgenerational inheritance on the next generations mediated by epigenetic mechanisms. Physical exercise is one potent intervention driving robust improvements of cognition and brain health, also inducing intergenerational transmission to the litter. However, little is known about whether exercise effects may be transgenerationally transmitted. Here we analyzed the adult hippocampal neurogenesis (AHN) and the behavioral phenotype of sedentary adult male mice of the F2 generation of exercised grandfathers (F0, patrilineal design). Both F1 and F2 were sedentary, while F0 performed a moderate exercise training. We found that the F2 mice from exercised F0 acquired and recalled both spatial and non-spatial information better than F2 from sedentary F0. Contextual fear conditioning resulted not affected, together with no differences in the AHN markers. These results demonstrate that the transgenerational transmission of the effects of exercise on specific cognitive tasks persists after two generations, even though some of the cellular changes induced in F1 disappear in F2, and suggest that moderate exercise training has a longer-lasting effect than previously thought, and this aspect is worth taking into account in public health programs. Comparative profiling analysis of miRNA-seq data of F2 generation of exercised grandfathers (F0, patrilineal design) vs F2 generation of sedentary grandfathers.