Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury

Exp Neurol. 2005 Jun;193(2):411-9. doi: 10.1016/j.expneurol.2005.01.015.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • CREB-Binding Protein
  • Enzyme-Linked Immunosorbent Assay / methods
  • GAP-43 Protein / genetics
  • GAP-43 Protein / metabolism
  • Immunohistochemistry / methods
  • Male
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Neuronal Plasticity / physiology*
  • Neurotrophin 3 / genetics
  • Neurotrophin 3 / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Physical Conditioning, Animal*
  • RNA, Messenger / biosynthesis
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / rehabilitation*
  • Synapsins / genetics
  • Synapsins / metabolism
  • Time Factors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Brain-Derived Neurotrophic Factor
  • GAP-43 Protein
  • Nerve Growth Factors
  • Neurotrophin 3
  • Nuclear Proteins
  • RNA, Messenger
  • Synapsins
  • Trans-Activators
  • CREB-Binding Protein
  • Crebbp protein, rat