Exercise normalizes levels of MAG and Nogo-A growth inhibitors after brain trauma.
Myelin is a major obstacle for axonal growth after CNS injury, to the extent that it is crucial to develop interventions to counteract postinjury growth inhibition and foster neural repair. We have studied the effects of the fluid percussion injury (FPI) model of traumatic brain injury (TBI) on protein levels of two myelin-associated molecules, myelin-associated glycoprotein (MAG) and Nogo-A, in the adult rat. We found that FPI elevated hippocampal levels of MAG and Nogo-A. Given the beneficial effects of exercise on CNS function, we evaluated the capacity of exercise to reduce these myelin-derived proteins after FPI. One week of voluntary running wheel exercise overcame the injury-related increase in MAG and Nogo-A. The action of brain-derived neurotrophic factor (BDNF) has been associated with exercise as well as with the modulation of growth inhibition in vitro. We found that the selective blockade of BDNF using the immunoadhesive chimera TrkB-IgG abolished the effects of exercise on MAG and Nogo-A. FPI reduced levels of growth-associated protein 43 (GAP-43), a marker of axonal growth, and synaptophysin (SYP), an indicator of synaptic growth. Exercise counteracted the effects of FPI on GAP-43 and SYP, while BDNF blockade abolished these effects of exercise. 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 prevented by BDNF blockade. These results indicate that exercise promotes a permissive cellular environment for repair after TBI, in a process in which BDNF plays a central role.
Chytrova
Gabriela
G
Department of Physiological Science, UCLA, 621 Charles E. Young Drive, Los Angeles, CA 90095, USA.
Ying
Zhe
Z
Gomez-Pinilla
Fernando
F
D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage; D008297:Male; D008954:Models, Biological; D009185:Myelin Proteins / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D000070798:Nogo Proteins; D010805:Physical Conditioning, Animal / Q000379:methods*; D011312:Pressure / Q000009:adverse effects; D011897:Random Allocation; D051381:Rats; D020813:Receptor, trkB / Q000276:immunology; D016708:Synaptophysin / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D007074:Immunoglobulin G; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat; D016708:Synaptophysin; D020813:Receptor, trkB; D017868:Cyclic AMP-Dependent Protein Kinases