Exercise Physiology Project
Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor that is expressed in skeletal muscle and affects peripheral motor neurons. Treatment with GDNF rescues motor neurons from axotomy-induced cell death and decreases loss of motor neurons in animal models of motor neuropathy and degeneration. Alterations in GDNF expression have been observed in skeletal muscle from individuals with amyotrophic lateral sclerosis, polymyositis or Duchenne type muscular dystrophy.
The long-term goals of these studies are to understand the mechanisms underlying the normal control of GDNF expression in skeletal muscle. The hypothesis being tested posits that expression of GDNF in skeletal muscle is linked to neuromuscular activity.
Two specific aims are addressed in these studies. Aim 1) Increased physical exercise will lead to elevated expression of GDNF in skeletal muscle. Aim 2) Decreased levels of physical activity will lead to decreased expression of GDNF in skeletal muscle.
For these studies GDNF expression will be examined in vivo in muscles from control rats (sedentary controls) and in rats following increased physical activity (treadmill training) or decreased physical activity (hindlimb suspension). Localization of GDNF protein will be examined using immunocytochemical techniques. Quantification of GDNF protein in cell culture medium and skeletal muscle tissue will be accomplished using ELISA. Expression of GDNF mRNA will be examined using quantitative, real-time polymerase chain reaction (PCR) methods.
Understanding the normal regulatory processes controlling GDNF expression will aid in understanding how these processes may become disturbed with aging, injury or in neurodegenerative diseases. Findings of these studies will help to identify potential sites for pharmacological intervention, to help slow or reverse abnormal changes occurring with injury or disease.