Journal of Applied Physiology AJP: Advances in Physiology Education
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J Appl Physiol 105: 1585-1594, 2008. First published September 18, 2008; doi:10.1152/japplphysiol.90775.2008 Free Article
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Exercise enhances the proliferation of neural stem cells and neurite growth and survival of neuronal progenitor cells in dentate gyrus of middle-aged mice

Chih-Wei Wu,1 Ya-Ting Chang,2 Lung Yu,1,3,4 Hsiun-ing Chen,1,4 Chauying J. Jen,1,4 Shih-Ying Wu,2 Chen-Peng Lo,1 and Yu-Min Kuo1,2

1Institute of Basic Medical Sciences, 2Department of Cell Biology and Anatomy, 3Institute of Behavioral Medicine, and 4Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan

Submitted 17 June 2008 ; accepted in final form 14 September 2008

Aging is an important determinant of adult hippocampal neurogenesis as the proliferation of neural stem/precursor cells (NSCs) declines dramatically before middle age. Contrary to this, physical exercise is known to promote adult hippocampal neurogenesis. The objective of this study is to investigate the effects of mandatory treadmill running (TR) on neurogenesis, including 1) NSCs proliferation, 2) neurite outgrowth of neuronal progenitor cells, and 3) the survival of newborn neurons in dentate area of middle-aged animals. Compared with 3-mo-old mice, numbers of mitotic cells and neuronal progenitor cells decreased dramatically by middle age and remained at low levels after middle age. Five weeks of TR not only increased NSC proliferation and the number of immature neurons but also promoted the maturation and survival of immature neurons in middle-aged mice. The neurogenic and neurotrophic effects of TR were not due to the reduction of the age-related elevation of serum corticosterone. Significantly, 5 wk of TR restored the age-dependent decline of brain-derived neurotrophic factor and its receptor, TrkB, which are known to promote neuronal differentiation and survival. Taken together, mandatory running exercise alters the brain chemistries of middle-aged animals toward an environment that is favorable to NSC proliferation, survival, and maturation.

middle age; brain-derived neurotrophic factor; survival


Address for reprint requests and other correspondence: Y.-M. Kuo, Dept. of Cell Biology and Anatomy, National Cheng Kung Univ. Medical College. 1 Ta Hsueh Rd., Tainan, Taiwan 70101 (e-mail address: kuoym{at}mail.ncku.edu.tw)






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