Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury.
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.
Ying
Zhe
Z
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.
Roy
Roland R
RR
Edgerton
V Reggie
VR
Gómez-Pinilla
Fernando
F
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
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