Running exerts a robust beneficial effect in a mouse model with impared neurogenesis, by shorthening the cell cycle lenght of neural stem and progenitor cell

Exposure to exercise increases the generation of new neurons in the adult neurogenesis. However, only few studies have investigated the beneficial effect of physical exercise in impaired neurogenesis paradigms. Here we use a mouse model in which the ablation of Btg1 produces a post?natal transient increase of hippocampal neurogenesis, followed by severe depletion of stem and progenitor cells during the adulthood. In this study, we examine whether running could reverse the severe phenotype observed in the adult Btg1 knockout mouse. To this aim, for the first time we evaluate how running influences the cell cycle kinetics of distinct stem and precursor subpopulations of wild type and Btg1 knockout mice, by adopting a recently developed method to measure the cell cycle length. Our data shown that running fully restores the proliferation in the Btg1 knockout mice, by shortening the S?phase length and consequently the overall cell cycle duration of stem (Sox2) and progenitor (Neurod1) cells. Conversely, in the wild?type mice exercise affects exclusively the cell cycle lengthening of NeuroD1 positive progenitor cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in the Btg1 null early postnatal mice and to completely replenish the loss of adult neurogenesis. The sustained increase of cell proliferation in Btg1 null mice after running provides a large pool of activated neural stem cells that results in a long?lasting increment of differentiation, production and survival of newborn neurons. This study shows for the first time that running changes cell cycle kinetics of newly?generated neurons in adult hippocampus.