Aging of the striatum: mechanisms and interventions.

Motor function declines with increasing adult age. Proper regulation of the balance between dopamine (DA) and acetylcholine (ACh) in the striatum has been shown to be fundamentally important for motor control. Although other factors can also contribute to this age-associated decline, a decrease in the concentration and binding potential of the DA D(2) receptor subtype in the striatum, especially in the cholinergic interneurons, are involved in the mechanism. Our studies have shown that gene transfer of the DA D(2) receptor subtype with adenoviral vectors is effective in ameliorating age-associated functional decline of the striatal cholinergic interneurons. These achievements confirm that an age-associated decrease of D(2)R contributes functional alteration of the interaction of DA and ACh in the striatum and demonstrate that these age-associated changes indeed are modifiable.