Aging of the rat mesostriatal system: differences between the nigrostriatal and the mesolimbic compartments

The impairment of the mesostriatal dopaminergic system has been considered responsible for motor and affective disturbances associated with aging and a risk factor for Parkinson's disease. However, the basic mechanisms underlying this phenomenon are still unknown. Here we used biochemical, molecular and morphological techniques directed at detecting flaws in the dopamine synthesis route and signs of dopaminergic degeneration in the rat mesostriatal system during normal aging. We found two different age-related processes. One is characterized by a dopa decarboxylase decrease, and involves both the nigrostriatal and mesolimbic compartments, and is responsible for a moderate dopamine loss in the dorsal striatum, where other parameters of dopamine synthesis are not affected. The other is characterized by axonal degeneration with aggregation of phosphorylated forms of tyrosine hydroxylase (TH) and amyloid precursor protein in degenerate terminals, and alpha-synuclein in their original somata. This process is restricted to mesolimbic regions and is responsible for the decline of TH activity and l-dopa levels and the greater decrease in dopamine levels in this compartment. These findings suggest that both the nigrostriatal and the mesolimbic systems are vulnerable to aging, but in contrast to what occurs in Parkinson's disease, the mesolimbic system is more vulnerable to aging than the nigrostriatal one.