Forced Limb-Use Studies in Rats May Have Implications for Parkinson's Disease

Gary W. Miller, Ph.D.
University of Texas at Austin
R01ES09248

Background: Parkinson's Disease patients experience progressive and severe motor impairment which is caused by the loss of dopamine producing neurons in the substantia nigra region of the brain. Behavioral and neurological changes may delay or mask the appearance of symptoms until the neurological damage becomes extensive enough to overwhelm these compensating mechanisms. As the disease progresses, patients tend to rely more on less affected limbs to make movement easier. Over time, conventional treatments lose their efficacy in relieving symptoms, movement becomes more difficult, and inactivity becomes more prominent.

Advance: Laboratory rats were surgically administered the neurotoxin 6-hydroxydopamine to one side of their brains resulting in the impairment of the forelimb on the opposite of their bodies. The animals were fitted with casts on their unaffected forelimb making them use the affected limb to move and support their weight. Animals fitted with the casts within one day of the experimental procedure were able to use the leg normally once the casts were removed. In addition, all tests for dopamine concentration and metabolism were normal suggesting a decrease in the degeneration of the dopamine producing neurons.

Implication: These findings suggest that physical therapy and exercise may have major effects on the quality of life for Parkinson's patients. Improvements in the movement of affected limbs should be expected, but more importantly, therapy may delay or prevent the loss of dopamine producing neurons which is the goal of current treatments.

Publication: Tillerson JL, Cohen AD, Philhower J, Miller GW, Zigmond MJ, Schallert T. Forced limb-use effects on the behavioral and neurochemical effects of 6-hydroxydopamine. J Neurosci. 2001 Jun 15;21(12):4427-35.