Melatonin potentiates running wheel-induced neurogenesis in the dentate gyrus of adult C3H/HeN mice hippocampus

This study assessed the role of melatonin in modulating running wheel(RW)-induced hippocampal neurogenesis in adult C3H/HeN mice. Chronic melatonin (0.02mg/mL, oral for 12days) treatment did not affect cell proliferation or cell survival determined by the number of BrdU-positive cells in dentate gyrus of mice with access to fixed wheel (FW). RW activity significantly increased cell proliferation [RW (n=8) versus FW (n=6): dorsal, 199 +/- 18 versus 125 +/- 12, P<0.01; ventral, 211 +/- 15 versus 123 +/- 13, P<0.01] and newborn cell survival [RW (n=7) versus FW (n=8): dorsal, 45 +/- 8.5 versus 15 +/- 1.8, P<0.01; ventral, 48 +/- 8.1 versus 15 +/- 1.4)] in the dorsal and ventral dentate gyrus. Oral melatonin treatment further potentiated RW activity-induced cell survival in both areas of the dentate gyrus [melatonin (n=10) versus vehicle (n=7): dorsal, 63 +/- 5.4 versus 45 +/- 8.5 P<0.05; ventral, 75 +/- 7.9 versus 48 +/- 8.1, P<0.01] and neurogenesis [melatonin (n=8) versus vehicle (n=8): dorsal, 46 +/- 3.4, versus 34 +/- 4.5, P<0.05; ventral, 41 +/- 3.4 versus 25 +/- 2.4, P<0.01]. We conclude that melatonin potentiates RW-induced hippocampal neurogenesis by enhancing neuronal survival suggesting that the combination of physical exercise and melatonin may be an effective treatment for diseases affecting the hippocampus neurogenesis.