Submitted on June 17, 2008
Revised on September 8, 2008
Accepted on September 14, 2008
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 Wu1, Ya-Ting Chang2, Lung Yu2, Hsiun-ing Chen3, Chauying J. Jen2, Shih-Ying Wu2, Chen-Peng Lo2, and Yu-Min Kuo2*
1 Institute of Basic Medical Sciences, National Cheng Kung University
2 National Cheng Kung University
3 National Cheng-Kung University
* To whom correspondence should be addressed. E-mail: kuoym{at}mail.ncku.edu.tw.
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 to 3-month-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 NSCs 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, five weeks of TR restored the age-dependent decline of brain derived neurotrophic factor (BDNF) 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 animal toward an environment that is favorable to NSCs proliferation, survival and maturation.
