Locomotor activity is beneficial in maintaining and improving neural function. Trophic factors are critical promoters of neural plasticity, and locomotor activity increases the expression of neurotrophic factors and their receptors in the brain, spinal cord and skeletal muscle. Thus, activity-induced increases in the expression of neurotrophic factors may be the molecular mechanism whereby exercise affects neural function. The PI proposes to use a well-defined exercise model to evaluate the effects of motor patterns on the expression of brain derived neurotrophic (BDNF) and neurotrophin 3 (NT-3) and their receptors in the spinal cord, dorsal root ganglia and skeletal muscle. To understand how locomotion can induce neurotrophins, the PI will determine whether the expression of neurotrophic factors is specific to a fixed rate of treadmill exercise and to the neural activity of those networks specifically associated with a particular motor pattern. In addition, the PI will determine whether the modulation of the neurotrophic factors depends on active contractile events in slow or fast extensors muscles (by injecting botulinum toxin into the muscle and assessing the impact on neurotrophic factors). Thirdly, the PI will determine whether locomotor deficit caused by degeneration of large muscle afferents (by using high doses of pyridoxine) can be countered by daily locomotion induction of neurotrophins.
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