The Novel Impact Of Treadmill Exercise And Sex Difference On Cell Proliferation and Cell Survival In The Dentate Gyrus Of G93A Mice

Neurogenesis persists in the adult mammalian brain and can be regulated by physiological stressors influencing cell proliferation or cell survival. We investigated whether sex and treadmill running would affect cell proliferation and newborn cell survival in the dentate gyrus (DG) of G93A mice, a transgenic model over‐expressing mutant human Cu/Zn‐superoxide dismutase (SOD1) and leading to excessive oxidative stress. Proliferating and surviving cells were labeled with bromodeoxyuridine (BrdU) over 7‐days before sacrificing mice @ 1 and 3 weeks. Proliferating cells were significantly higher in males than in females (p=0.009) but cell survival tended to be higher in female vs. male G93A mice (p=0.057). Running G93A mice have less proliferating cells than sedentary G93A mice (p=0.056); however, running wild type mice have significantly more proliferating cells than sedentary wild type mice (p=0.036) and than running G93A mice (p=0.040). In addition, female running G93A mice displayed more surviving cells than male running G93A mice (p=0.033). Wild type running mice showed a significant increase in cell survival vs. sedentary wild type (p=0.028). These results suggested that running promotes cell proliferation in wild type mice, but inhibits cell proliferation in G93A mice. Running promotes cell survival in male and female wild type and only female G93A mice. The sex differences in cell proliferation and survival for the G93A mice are supportive of our previous observation that female G93A mice have better survival and resistance to excessive running stress as compared with males.