GDNF and Motor Related Striatal Activity in Aged Rats

Aging is associated with decreased motor function in humans and in animals. Bradykinesia and disturbances of posture and gait have been related to an increased risk of death in the elderly. The similarity of these motor deficits to the symptoms of Parkinson's disease implicates functional changes in the nigrostriatal dopamine (DA) system. These changes, which include a decreased number of DA receptors and diminished evoked DA release and uptake, may contribute to the altered striatal electrophysiological activity that we have recently reported in freely-moving aged Fischer 344 (F344) rats. These electrophysiological alterations may in turn contribute to the progressive deterioration of movement that occurs in aging. Studies conducted in this lab and in others have demonstrated that age-related alterations in movement capacity and DA function can be reversed by the administration of glial cell line-derived neurotrophic factor (GDNF). The purpose of this pilot grant is to determine the effects of GDNF on altered locomotor-related striatal electrophysiological activity in aged (24-month-old) F344 rats. Animals will be behaviorally-characterized with regard to locomotor activity so that relationships between electrophysiology and behavior can be determined. These studies should yield novel and valuable information regarding the physiological basis of GDNF's antiparkinsonian effects.