Exercise-induced promotion of hippocampal cell proliferation requires beta-endorphin.
Adult hippocampal neurogenesis is influenced by a variety of stimuli, including exercise, but the mechanisms by which running affects neurogenesis are not yet fully understood. Because beta-endorphin, which is released in response to exercise, increases cell proliferation in vitro, we hypothesized that it could exert a similar effect in vivo and mediate the stimulatory effects of running on neurogenesis. We thus analyzed the effects of voluntary wheel-running on adult neurogenesis (proliferation, differentiation, survival/death) in wild-type and beta-endorphin-deficient mice. In wild-type mice, exercise promoted cell proliferation evaluated by sacrificing animals 24 h after the last 5-bromo-2'-deoxyuridine (BrdU) pulse and by using endogenous cell cycle markers (Ki67 and pH(3)). This was accompanied by an increased survival of 4-wk-old BrdU-labeled cells, leading to a net increase of neurogenesis. Beta-endorphin deficiency had no effect in sedentary mice, but it completely blocked the running-induced increase in cell proliferation; this blockade was accompanied by an increased survival of 4-wk-old cells and a decreased cell death. Altogether, adult neurogenesis was increased in response to exercise in knockout mice. We conclude that beta-endorphin released during running is a key factor for exercise-induced cell proliferation and that a homeostatic balance may regulate the final number of new neurons.
Koehl
M
M
Centre de Recherche INSERM U862, Physiopathologie de la Plasticité Neuronale, 146 Rue Léo Saignat, 33077 Bordeaux Cedex, France. koehl@bordeaux.inserm.fr
Meerlo
P
P
Gonzales
D
D
Rontal
A
A
Turek
F W
FW
Abrous
D N
DN
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D003433:Crosses, Genetic; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D010805:Physical Conditioning, Animal; D012420:Running; D001615:beta-Endorphin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*
D001615:beta-Endorphin; D001973:Bromodeoxyuridine