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GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE
A Journal on Internal Medicine and Pharmacology
Indexed/Abstracted in: BIOSIS Previews, EMBASE, Scopus, Emerging Sources Citation Index
Gazzetta Medica Italiana Archivio per le Scienze Mediche 2014 June;173(6):329-40
Intense exercise enhances the hippocampal proliferation of progenitor cells via activating the Flk1 signaling cascade in mice
Lee H. 1, Kiuchi T. 3, Muto J. 2, Ohta S. 1, Mikami T. 3
1 Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kosugi‑machi, Nakahara‑ku, Kawasaki, Kanagawa, Japan;
2 Graduate School of Health and Sport Science, Nippon Sport Science University, Fukasawa, Setagaya‑ku, Tokyo, Japan;
3 Department of Health and Sports Science, Nippon Medical School, Kosugi‑machi, Nakahara‑ku, Kawasaki, Kanagawa, Japan
AIM: Much attention to regularly performing exercise at low or moderate intensity has been paid on the stimulation of adult hippocampal neurogenesis. Here, we focused on the contribution of high-intensity exercise to the hippocampal proliferation.
METHODS: To examine effect of single exercise on the hippocampal proliferation and the brain-derived neurotrophic factor (BDNF) expression, mice were subjected to intense running on a treadmill with gradual increases of treadmill speed until exhaustion or 60 min of moderate running. Additionally, to reveal the involvement of vascular endothelial growth factor (VEGF)-receptor 2 (Flk1) signaling cascade on the hippocampal proliferation and BDNF expression, an Flk1 inhibitor, SU1498 was intraperitoneally administered before exercise.
RESULTS: A single bout of intense exercise significantly increased expression of BDNF, accompanying the stimulation of the hippocampal proliferation of newborn cells. SU1498 (a specific inhibitor of VEGF receptor 2) suppressed the hippocampal proliferation of newborn cells as well as the BDNF expression. Moreover, a single bout of intense exercise induced the phosphorylations of the Flk1, extracellular signal-regulated kinases (ERKs) and cAMP response element-binding protein (CREB), all of which are involved in the VEGF-Flk1 cascade. On the other hand, a single bout of moderate exercise did not influence the hippocampal proliferation and the BDNF expression.
CONCLUSION: These findings suggest that intense exercise-induced the hippocampal proliferation of newborn cells is regulated by BDNF under the VEGF-Flk1 signaling cascade. This study highlights that not only regularly performing moderate exercise but also a single bout of intense exercise also exhibits neurotrophic effects.