PMID- 17497667 OWN - NLM STAT- MEDLINE DCOM- 20070725 LR - 20220316 IS - 0894-1491 (Print) IS - 1098-1136 (Electronic) IS - 0894-1491 (Linking) VI - 55 IP - 9 DP - 2007 Jul TI - Exercise decreases myelin-associated glycoprotein expression in the spinal cord and positively modulates neuronal growth. PG - 966-75 AB - To successfully grow, neurons need to overcome the effects of hostile environments, such as the inhibitory action of myelin. We have evaluated the potential of exercise to overcome the intrinsic limitation of the central nervous system for axonal growth. In line with the demonstrated ability of exercise to increase the regenerative potential of neurons, here we show that exercise reduces the inhibitory capacity of myelin. Cortical neurons grown on myelin from exercised rats showed a more pronounced neurite extension compared with neurons grown on poly-D-lysine, or on myelin extracted from sedentary animals. The activity of cyclin-dependent kinase 5, a kinase involved in neurite outgrowth, was found to be increased in cortical neurons grown on exercise-myelin and in the lumbar spinal cord enlargement of exercised animals. Exercise significantly decreased the levels of myelin-associated glycoprotein (MAG), a potent axonal growth inhibitor, suggesting that downregulation of MAG is part of the mechanism through which exercise reduces growth inhibition. It is known that exercise elevates brain-derived neurotrophic factor (BDNF) spinal cord levels and that BDNF acts to overcome the inhibitory effects of myelin. Accordingly, we blocked the action of BDNF during exercise, which suppressed the exercise-related MAG decrease. Protein kinase A (PKA) has been related to the ability of BDNF to overcome growth inhibition; in agreement, we found that exercise increased PKA levels and this effect was reverted by blocking BDNF. Overall, these results show that exercise promotes a permissive cellular environment for axonal growth in the adult spinal cord requiring BDNF action. CI - (c) 2007 Wiley-Liss, Inc. FAU - Ghiani, Cristina A AU - Ghiani CA AD - Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Neurobiology and Psychiatry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. FAU - Ying, Zhe AU - Ying Z FAU - de Vellis, Jean AU - de Vellis J FAU - Gomez-Pinilla, Fernando AU - Gomez-Pinilla F LA - eng GR - R01 NS045804/NS/NINDS NIH HHS/United States GR - NS45804/NS/NINDS NIH HHS/United States GR - HD04612/HD/NICHD NIH HHS/United States GR - HD06576/HD/NICHD NIH HHS/United States GR - P01 HD006576/HD/NICHD NIH HHS/United States GR - R01 NS050465/NS/NINDS NIH HHS/United States GR - P30 HD004612/HD/NICHD NIH HHS/United States GR - R01 NS050465-02/NS/NINDS NIH HHS/United States GR - NS050465/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Glia JT - Glia JID - 8806785 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Growth Inhibitors) RN - 0 (Myelin-Associated Glycoprotein) RN - EC 2.7.11.1 (Cyclin-Dependent Kinase 5) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.22 (Cdk5 protein, rat) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/metabolism MH - Cell Differentiation/physiology MH - Cells, Cultured MH - Cerebral Cortex/cytology/drug effects/metabolism MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Cyclin-Dependent Kinase 5/metabolism MH - Down-Regulation/physiology MH - Growth Cones/drug effects/*metabolism MH - Growth Inhibitors/metabolism MH - Male MH - Myelin Sheath/*metabolism MH - Myelin-Associated Glycoprotein/*metabolism MH - Nerve Regeneration/drug effects/physiology MH - Neuronal Plasticity/drug effects/physiology MH - Physical Conditioning, Animal/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Spinal Cord/cytology/*metabolism MH - Up-Regulation/physiology PMC - PMC2805662 MID - NIHMS161109 EDAT- 2007/05/15 09:00 MHDA- 2007/07/26 09:00 PMCR- 2010/01/12 CRDT- 2007/05/15 09:00 PHST- 2007/05/15 09:00 [pubmed] PHST- 2007/07/26 09:00 [medline] PHST- 2007/05/15 09:00 [entrez] PHST- 2010/01/12 00:00 [pmc-release] AID - 10.1002/glia.20521 [doi] PST - ppublish SO - Glia. 2007 Jul;55(9):966-75. doi: 10.1002/glia.20521.