Physical exercise is well known for its positive effects on general health (specifically, on brain function and health), and some mediating mechanisms are also known. A few reports have addressed intergenerational inheritance of some of these positive effects from exercised mothers or fathers to the progeny, but with scarce results in cognition. We report here the inheritance of moderate exercise-induced paternal traits in offspring’s cognition, neurogenesis, and enhanced mitochondrial activity. These changes were accompanied by specific gene expression changes, including gene sets regulated by microRNAs, as potential mediating mechanisms. We have also demonstrated a direct transmission of the exercise-induced effects through the fathers’ sperm, thus showing that paternal physical activity is a direct factor driving offspring’s brain physiology and cognitive behavior.Abstract
Physical exercise has positive effects on cognition, but very little is known about the inheritance of these effects to sedentary offspring and the mechanisms involved. Here, we use a patrilineal design in mice to test the transmission of effects from the same father (before or after training) and from different fathers to compare sedentary- and runner-father progenies. Behavioral, stereological, and whole-genome sequence analyses reveal that paternal cognition improvement is inherited by the offspring, along with increased adult neurogenesis, greater mitochondrial citrate synthase activity, and modulation of the adult hippocampal gene expression profile. These results demonstrate the inheritance of exercise-induced cognition enhancement through the germline, pointing to paternal physical activity as a direct factor driving offspring’s brain physiology and cognitive behavior.