AGING OF CENTRAL DOPAMINERGIC SYSTEMS IN PRIMATES

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Increasing problems with rigidity, bradykinesia, tremor and gait disturbances are seen with advancing age. These movement dysfunctions are associated with a significant increase in morbidity and mortality in the elderly. Our studies in rhesus monkeys will initially focus on delineating the relationship between age-associated changes in the nigrostriatal system and the decline in motor functions during normal aging processes. Our research program project has been designed to critically test four hypotheses. Hypothesis 1: that rhesus monkeys undergo declines in motor functions which closely model those seen in humans. Hypothesis 2: that there is a gradual, continuous change in nigrostriatal dopaminergic function in rhesus monkeys with age. Hypothesis 3: that there is a gradual continuous loss of midbrain dopamine neurons in rhesus monkeys in aging. Hypothesis 4: that upregulation of the nigrostriatal dopaminergic system in older rhesus monkeys by intracerebral administrations of the potent dopaminergic trophic factor GDNF improve motor function. The program project is organized into three research projects which are supported by two core units. Project 1-3 are carefully integrated and coordinated to analyze motor functions and the nigrostriatal dopaminergic system in rhesus monkeys. An Administrative Core supports all three project, coordinating collection, pooling and analysis of data. A Primate Core Facility supervises and coordinates the use of all rhesus monkeys in these studies.