Voluntary Exercise Increases Oligodendrogenesis in Spinal Cord

ABSTRACT 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-day 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 effects of voluntary exercise as a possible co-treatment for spinal cord injury.

[1]  C. Cotman,et al.  Wheel running and fluoxetine antidepressant treatment have differential effects in the hippocampus and the spinal cord , 2007, Neuroscience.

[2]  Gerd Kempermann,et al.  Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus , 2006, Neurobiology of Aging.

[3]  F. Gage,et al.  Epidermal Growth Factor and Fibroblast Growth Factor-2 Have Different Effects on Neural Progenitors in the Adult Rat Brain , 1997, The Journal of Neuroscience.

[4]  V. Edgerton,et al.  Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord , 2003, Brain Research.

[5]  P. Eriksson,et al.  IGF-I has a direct proliferative effect in adult hippocampal progenitor cells , 2003, Molecular and Cellular Neuroscience.

[6]  I. Torres-Aleman,et al.  Circulating Insulin-Like Growth Factor I Mediates the Protective Effects of Physical Exercise against Brain Insults of Different Etiology and Anatomy , 2001, The Journal of Neuroscience.

[7]  R. Armstrong,et al.  Brain norepinephrine and metabolites after treadmill training and wheel running in rats. , 1996, Medicine and science in sports and exercise.

[8]  F. Castro,et al.  The molecular orchestra of the migration of oligodendrocyte precursors during development , 2005, Brain Research Reviews.

[9]  L. Weiner,et al.  Neural Stem Cells , 2008, Methods in Molecular Biology™.

[10]  S. Weiss,et al.  Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. , 1992, Science.

[11]  J. Winkler,et al.  Analysis of neurogenesis and programmed cell death reveals a self-renewing capacity in the adult rat brain , 2000, Neuroscience Letters.

[12]  D. van der Kooy,et al.  Transforming Growth Factor-α Null and Senescent Mice Show Decreased Neural Progenitor Cell Proliferation in the Forebrain Subependyma , 1997, The Journal of Neuroscience.

[13]  V. Edgerton,et al.  Differential regulation by exercise of BDNF and NT‐3 in rat spinal cord and skeletal muscle , 2001, The European journal of neuroscience.

[14]  W. Richardson,et al.  Oligodendrocyte Population Dynamics and the Role of PDGF In Vivo , 1998, Neuron.

[15]  M. Carson,et al.  Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. , 1993, Neuron.

[16]  W. Richardson,et al.  A role for platelet-derived growth factor in normal gliogenesis in the central nervous system , 1988, Cell.

[17]  Brent A. Reynolds,et al.  Neural stem cells in the adult mammalian forebrain: A relatively quiescent subpopulation of subependymal cells , 1994, Neuron.

[18]  W. Snider,et al.  PDGF A-chain gene is expressed by mammalian neurons during development and in maturity , 1991, Cell.

[19]  J. Collins,et al.  Cell cycle and proliferation dynamics of adult rat oligodendrocytes , 1992, Journal of neuroscience research.

[20]  H. Kettenmann,et al.  Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes , 2003, Molecular and Cellular Neuroscience.

[21]  Eiji Kobayashi,et al.  Oligodendrocytes and Radial Glia Derived From Adult Rat Spinal Cord Progenitors: Morphological and Immunocytochemical Characterization , 2007, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[22]  F. Gomez-Pinilla,et al.  Exercise decreases myelin‐associated glycoprotein expression in the spinal cord and positively modulates neuronal growth , 2007, Glia.

[23]  K. Asakura,et al.  Neurotrophin-4/5 promotes proliferation of oligodendrocyte-type-2 astrocytes (O-2A). , 2000, Brain research. Developmental brain research.

[24]  F. Mcmorris,et al.  Insulin‐like growth factor I promotes cell proliferation and oligodendroglial commitment in rat glial progenitor cells developing in vitro , 1988, Journal of neuroscience research.

[25]  J. Rafols,et al.  Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke. , 2004, Current neurovascular research.

[26]  Brent A. Reynolds,et al.  Multipotent CNS Stem Cells Are Present in the Adult Mammalian Spinal Cord and Ventricular Neuroaxis , 1996, The Journal of Neuroscience.

[27]  P. Eriksson,et al.  Extended voluntary running inhibits exercise-induced adult hippocampal progenitor proliferation in the spontaneously hypertensive rat. , 2005, Journal of neurophysiology.

[28]  Mitsuhiko Masuhara,et al.  Effects of chronic treadmill running on neurogenesis in the dentate gyrus of the hippocampus of adult rat , 2006, Brain Research.

[29]  C. Cotman,et al.  Exercise and brain neurotrophins , 1995, Nature.

[30]  F. Gage,et al.  Proliferation and Differentiation of Progenitor Cells Throughout the Intact Adult Rat Spinal Cord , 2000, The Journal of Neuroscience.

[31]  C. Cotman,et al.  Exercise: a behavioral intervention to enhance brain health and plasticity , 2002, Trends in Neurosciences.

[32]  I. Torres-Aleman,et al.  Circulating Insulin-Like Growth Factor I Mediates Effects of Exercise on the Brain , 2000, The Journal of Neuroscience.

[33]  Adam R Ferguson,et al.  BDNF and learning: Evidence that instrumental training promotes learning within the spinal cord by up-regulating BDNF expression , 2007, Neuroscience.

[34]  D. van der Kooy,et al.  In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  K. Jin,et al.  Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[36]  C. Cotman,et al.  Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain , 1996, Brain Research.

[37]  M. Müller,et al.  Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary-adrenocortical axis. , 2003, Endocrinology.

[38]  Roland R Roy,et al.  Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. , 2002, Journal of neurophysiology.

[39]  M. Skup,et al.  Long-Term Locomotor Training Up-Regulates TrkBFL Receptor-like Proteins, Brain-Derived Neurotrophic Factor, and Neurotrophin 4 with Different Topographies of Expression in Oligodendroglia and Neurons in the Spinal Cord , 2002, Experimental Neurology.

[40]  E. Van Obberghen,et al.  Expression of IGF‐I and insulin receptor genes in the rat central nervous system: A developmental, regional, and cellular analysis , 1991, Journal of neuroscience research.

[41]  R. Bansal,et al.  Specific inhibitor of FGF receptor signaling: FGF‐2‐mediated effects on proliferation, differentiation, and MAPK activation are inhibited by PD173074 in oligodendrocyte‐lineage cells , 2003, Journal of neuroscience research.

[42]  T J Sejnowski,et al.  Running enhances neurogenesis, learning, and long-term potentiation in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[43]  V. Edgerton,et al.  Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury , 2005, Experimental Neurology.

[44]  C. Cotman,et al.  Exercise-induced gene expression changes in the rat spinal cord. , 2005, Gene expression.

[45]  Activation, Proliferation and Commitment of Endogenous Stem/Progenitor Cells to the Oligodendrocyte Lineage by TS1 in a Rat Model of Dysmyelination , 2006, Developmental Neuroscience.

[46]  Fred H. Gage,et al.  Neurotrophin-3 and Brain-Derived Neurotrophic Factor Induce Oligodendrocyte Proliferation and Myelination of Regenerating Axons in the Contused Adult Rat Spinal Cord , 1998, The Journal of Neuroscience.

[47]  F. Gomez-Pinilla,et al.  Physical exercise induces FGF-2 and its mRNA in the hippocampus , 1997, Brain Research.

[48]  M. Rao.  Multipotent and restricted precursors in the central nervous system , 1999, The Anatomical record.

[49]  M. Yamaguchi,et al.  Visualization of neurogenesis in the central nervous system using nestin promoter‐GFP transgenic mice , 2000, Neuroreport.

[50]  D. Schatz,et al.  Selective expression of RAG-2 in chicken B cells undergoing immunoglobulin gene conversion , 1991, Cell.

[51]  G. Kempermann,et al.  Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli , 2003, The Journal of comparative neurology.

[52]  F. Gage,et al.  Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus , 1999, Nature Neuroscience.

[53]  F. Gage,et al.  IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes , 2004, The Journal of cell biology.

[54]  P. Eriksson,et al.  Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[55]  K. McDermott,et al.  Differentiation of oligodendrocytes in neurospheres derived from embryonic rat brain using growth and differentiation factors , 2007, Journal of neuroscience research.

[56]  James P. McAllister,et al.  Increased astrocyte proliferation in rats after running exercise , 2005, Neuroscience Letters.

[57]  M. Carson,et al.  Insulin-like growth factor I increases brain growth and central nervous system myelination in tTransgenic mice , 1993, Neuron.

[58]  F. Gomez-Pinilla,et al.  Potential therapeutic effects of exercise to the brain. , 2007, Current medicinal chemistry.

[59]  W. Richardson,et al.  Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. , 1999, Development.

[60]  Robert H Miller.  Oligodendrocyte origins , 1996, Trends in Neurosciences.

[61]  T. Matsui,et al.  FGF modulates the PDGF-driven pathway of oligodendrocyte development , 1990, Neuron.

[62]  R. Galli,et al.  Neural Stem Cells: An Overview , 2003, Circulation research.