title: Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury.
abstract: We have conducted studies to determine the potential of exercise to benefit the injured spinal cord using neurotrophins. Adult rats were randomly assigned to one of three groups: (1) intact control (Con); (2) sedentary, hemisected at a mid-thoracic level (Sed-Hx), or (3) exercised, hemisected (Ex-Hx). One week after surgery, the Ex-Hx rats were exposed to voluntary running wheels for 3, 7, or 28 days. BDNF mRNA levels on the lesioned side of the spinal cord lumbar region of Sed-Hx rats were approximately 80% of Con values at all time points and BDNF protein levels were approximately 40% of Con at 28 days. Exercise compensated for the reductions in BDNF after hemisection, such that BDNF mRNA levels in the Ex-Hx rats were similar to Con after 3 days and higher than Con after 7 (17%) and 28 (27%) days of exercise. After 28 days of exercise, BDNF protein levels were 33% higher in Ex-Hx than Con rats and were highly correlated (r=0.86) to running distance. The levels of the downstream effectors for the action of BDNF on synaptic plasticity synapsin I and CREB were lower in Sed-Hx than Con rats at all time points. Synapsin I mRNA and protein levels were higher in Ex-Hx rats than Sed-Hx rats and similar to Con rats at 28 days. CREB mRNA values were higher in Ex-Hx than Sed-Hx rats at all time points. Hemisection had no significant effects on the levels of NT-3 mRNA or protein; however, voluntary exercise resulted in an increase in NT-3 mRNA levels after 28 days (145%). These results are consistent with the concept that synaptic pathways under the regulatory role of BDNF induced by exercise can play a role in facilitating recovery of locomotion following spinal cord injury.
authors.affiliation: Department of Physiological Science, UCLA, Los Angeles, CA 90095-1527, USA; Division of Neurosurgery, UCLA Brain Injury Research Center, Los Angeles, CA 90095-1527, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ying
authors.forename: Roland R
authors.initials: RR
authors.lastname: Roy
authors.forename: V Reggie
authors.initials: VR
authors.lastname: Edgerton
authors.forename: Fernando
authors.initials: F
authors.lastname: Gómez-Pinilla
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D050882:CREB-Binding Protein; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000534:rehabilitation*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016704:Synapsins; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat