Exercise-induced promotion of hippocampal cell proliferation requires beta-endorphin
The FASEB Journal. 2008-07-01; 22(7): 2253-2262
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1. FASEB J. 2008 Jul;22(7):2253-62. doi: 10.1096/fj.07-099101. Epub 2008 Feb 8.
Exercise-induced promotion of hippocampal cell proliferation requires
Koehl M(1), Meerlo P, Gonzales D, Rontal A, Turek FW, Abrous DN.
(1)Centre de Recherche INSERM U862, Physiopathologie de la Plasticité Neuronale,
146 Rue Léo Saignat, 33077 Bordeaux Cedex, France.
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.
PMID: 18263701 [Indexed for MEDLINE]