Regionally selective manifestations of neostriatal aging.

Presynaptic and postsynaptic markers of the cholinergic and dopaminergic systems have characteristic topographical distributions within the striatum. Aside from the dopaminergic afferents, several other afferent systems exhibit a heterogeneous distribution in the striatum. The net result is that each part of the striatum receives a specific and unique combination of afferents. Moreover, the intrinsic striatal systems also have unique distributions, so each part of the striatum consists of a unique combination of afferent and intrinsic neurotransmitter systems. In view of these points, one may expect that the striatum is functionally very complex, integrating information from a wide variety of brain areas. One may also assume from these facts that the striatum is a functionally heterogeneous structure. Consistent with that conclusion, behavioral and pharmacological studies show that interruption of neurotransmission in localized regions of the striatum produces very specific behavioral and physiological effects. Age-related neurochemical changes are also confined to specific striatal regions. Which regions are affected will depend on a variety of factors, including the neurochemical parameter studied and the species or strain of animal. However, we still do not know what factors make a particular striatal area vulnerable to the effects of aging or disease. Moreover, a question that remains to be answered is whether the regions that are affected by neurodegenerative diseases are the same ones affected during normal aging. If so, then this may provide a clue as to why neurodegenerative diseases of the basal ganglia increase in frequency with advancing age. Nevertheless, discrete regional neurochemical alterations may underlie specific symptoms of these diseases. Further study of this relationship may provide the basis for treatments that better target the source of the symptoms. Not only would this increase the effectiveness of the treatment, it would help reduce potential side effects. This may be particularly important, for example, with respect to the use of tissue explants in the treatment of diseases of the basal ganglia.