Exercise-induced promotion of hippocampal cell proliferation requires β-endorphin

• Published in: The FASEB journal Vol. 22; no. 7; pp. 2253 - 2262
• Main Authors: Koehl, M, Meerlo, P, Gonzales, D, Rontal, A, Turek, F.W, Abrous, D.N
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01-07-2008; Federation of American Society of Experimental Biology
• Subjects: adult neuro genesis; Animals; beta-Endorphin - deficiency; beta-Endorphin - genetics; beta-Endorphin - physiology; Bromodeoxyuridine - pharmacology; cell survival; Crosses, Genetic; Female; homeostatic balance; Life Sciences; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons and Cognition; opioids; Phenotype; Physical Conditioning, Animal; Running
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.07-099101

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 β-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 β-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 pH₃). This was accompanied by an increased survival of 4-wk-old BrdU-labeled cells, leading to a net increase of neurogenesis. β-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 β-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., Meerlo, P., Gonzales, D., Rontal, A., Turek, F. W., Abrous, D. N. Exercise-induced promotion of hippocampal cell proliferation requires β-endorphin.