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

Koehl, M., Meerlo, P., Gonzales, D., Rontal, A., Turek, F. W. & Abrous, D. N., 2008, In : The FASEB Journal. 22, p. 2253-2262

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DOI

  • M. Koehl
  • P. Meerlo
  • D. Gonzales
  • A. Rontal
  • F. W. Turek
  • D. N. Abrous

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.

Original languageEnglish
Pages (from-to)2253-2262
JournalThe FASEB Journal
Volume22
Publication statusPublished - 2008

    Keywords

  • hippocampus, dentate gyrus, stem cell, adult neurogenesis, cell proliferation, cell survival, cell death, apoptosis, pH3, BrdU, KI-67, doublecortin, voluntary exercise, physical activity, locomotion, voluntary running, running, running wheel , opioids, opioid receptor, mu-opioid receptor, endorphins, beta-endorphin, beta-endorphin deficient mice

ID: 4746258