Functional aging of the nigro-striatal system

Abstract

A number of movement disorders in the elderly are suggestive of age-associated extrapyramidal dysfunction. In addition, the onsets of two major movement disorders of better-known extrapyramidal pathophysiological locus, Huntington's chorea and Parkinson's disease, are highly age related. While slight to moderate declines in a number of presynaptic dopaminergic markers in the striatum have generally supported the view of declining dopaminergic function in the aged, a clear picture of the relationship between these biochemical parameters and function of this important extrapyramidal pathway has yet to emerge. Recent results from a number of laboratories representing combined behavioral, electrophysiological, and biochemical approaches have allowed a more analytical approach to the problem. First, age-related changes in this pathway appear to be coordinated between the pre- and post-synaptic components of the system. Dopamine receptor binding and dopamine-activated adenyl cyclase decrease at an earlier age and to a greater extent than do the presynaptic markers of the dopamine neurons themselves. Second, functional disorder of the nigro-striatal system may be more regulatory in nature than simple neuronal loss would suggest. Aging C57BL/6J mice, for example, did not show behavioral or biochemical supersensitivity following a chronic haloperidol regime which resulted in both phenomena in young- and middle-aged mice. Regulatory decreases in receptor number and response to dopamine agonists appear to be intact in the aging mouse. Lastly, the increased vulnerability of the elderly to seemingly incompatible motoric side-effects to the neuroleptic drugs indirectly suggest alterations in the control system parameters of the nigro-striatal pathway. Electrophysiological approaches are now opening this avenue of investigation.