By: Krityakiaranaa,b, A. Espinosa-Jeffreya, C.A. Ghiania, P. M. Zhaoa, F. Gomez-Pinillac, M.Yamaguchid, N. Kotchabhakdib, and J. de Vellisa
Intellectual and Developmental Disability Research Center, Semel Institute for Neuroscience and Human Behavior, Departments of Neurobiology and Psychiatry, David Geffen School of Medicine at UCLA, Los Angeles, CA bNeuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, 999 Phutthamonthol 4 Road, Salaya, Phutthamonthol, Nakornpathom 73170, Thailand cDepartment of Physiological Sciences and Department of Neurosurgery, University of California at Los Angeles, Los Angeles, CA dDepartment of Physiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Exercise has been shown to increase hippocampal neurogenesis, but the effects of exercise on oligodendrocyte generation have not yet been reported. In this study, we evaluated the hypothesis that voluntary exercise may affect neurogenesis, and more in particular, oligodendrogenesis, in the thoracic segment of the intact spinal cord of adult nestin-GFP transgenic mice. Voluntary exercise for 7 and 14 days increased nestin-GFP expression around the ependymal area. In addition, voluntary exercise for 7 days significantly increased nestin-GFP expression in both the white and gray matter of the thoracic segment of the intact spinal cord, whereas, 14 days-exercise decreased nestin-GFP expression. Markers for immature oligodendrocytes (Transferrin and CNPase) were significantly increased after 7 days of voluntary exercise. These results suggest that voluntary exercise positively influences oligodendrogenesis in the intact spinal cord, emphasizing the beneficial effect of voluntary exercise as a possible co-treatment for spinal cord injury.
Exercise; nestin; neurogenesis; oligodendrocyte
It is now widely established that the adult mammalian central nervous system (CNS) retains the ability of producing neural progenitor cells (NPC), an important feature in view of the continuous neural plasticity. The adult brain can display regenerative potential (Rao, 1999, Kulbatski et al., 2007). Proliferation, differentiation and survival of these NPC are regulated by many kinds of neurotrophic factors, which in turn, can be modulated by exercise (Reynolds and Weiss, 1992; Morshead et al., 1994; Craig et al., 1996; Weiss et al., 1996; Kuhn et al., 1997; Tropepe et al., 1997).
The beneficial effects of exercise on the brain and spinal cord have been extensively investigated and recognized (for review see: Ang and Gomez-Pinilla, 2007). Voluntary exercise increases neurogenesis in the adult rodent brain (van Praag et al., 1999a, b; Munehiro et al., 2006). It was also established that the beneficial effects of exercise are mediated by increased levels of the trophic factors brain derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) (Gomez-Pinilla et al., 2001, 2002, 2007; Skup et al., 2002; Ying et al., 2003, 2005).
Trophic factors, such as BDNF or IGF-I, drive and support NPC as well as oligodendrocytes (OL) development.
In the adult spinal cord, NPC may preferentially give rise to OL and radial glia (Cotman and Gerchtold, 2002; Perreau et al., 2005; Kublatski et al., 2007).
OL are glial cells that intermingle with neurons in the CNS and form myelin sheaths (de Castro and Brian, 2005). In the adult spinal cords, oligodendrocyte progenitors (OLP) can still be generated without differences in the rate of division or the persistence of dividing cells in the dorsal, lateral and ventral regions (Horner et al., 2000). Undetectable baseline levels of neurogenesis and oligodendrogenesis were reported in the intact adult spinal cord (Engesser- Cesar et al., 2007), suggesting the spinal cord has a very limited regenerative ability. The goal of the present study was to examine how voluntary exercise may influence neurogenesis in the intact spinal cord with a particular focus on the OLP lineage. In our work, we used voluntary exercise as a paradigm that closely applies to the human behavior and benefit (Dunn et al., 1996; Droste et al., 2003; Ghiani et al., 2007). We now show that voluntary exercise increases neurogenesis around the ependymal area in a time-dependent manner, and in particular increased immature OL in the intact spinal cord.