Elevation of striatal urate in experimental models of Parkinson's disease: a compensatory mechanism triggered by dopaminergic nigrostriatal degeneration?

Epidemiological studies have indicated an inverse association between high uricemia and incidence of Parkinson's disease (PD). To investigate the link between endogenous urate and neurotoxic changes involving the dopaminergic nigrostriatal system, this study evaluated the modifications in the striatal urate levels in two models of PD. To this end, a partial dopaminergic degeneration was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice, while a severe dopaminergic degeneration was elicited by unilateral medial forebrain bundle infusion of 6-hydroxydopamine (6-OHDA) in rats. Urate levels were measured by in vivo microdialysis at 7 or 14 days from toxin exposure. The results obtained demonstrated higher urate levels in the dopamine-denervated striatum of 6-OHDA-lesioned rats compared with the intact striatum. Moreover, an inverse correlation between urate and dopamine levels was observed in the same area. In contrast, only a trend to significant increase in striatal urate was observed in MPTP-treated mice. These results demonstrate that a damage to the dopaminergic nigrostriatal system elevates the striatal levels of urate, and suggest that this could be an endogenous compensatory mechanism to attenuate dopaminergic neurodegeneration. This finding may be important in light of the epidemiological and preclinical evidences that indicate a link between urate and development of PD.