Spontaneous long-term compensatory dopaminergic sprouting in MPTP-treated mice

The present study sought to determine whether severe 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication elicits spontaneous long-term compensatory sprouting in mice. Animals, once treated, were kept without further treatment for 0.5, 1, 5, or 7 months. The stability of the nigral degeneration was checked by evaluation of the number of tyrosine hydroxylase immunoreactive (TH-IR) neurons, whereas sprouting was assessed using both [(3)H]-dopamine (DA) uptake by striatal synaptosomes and optical density of TH-immunolabeled fibers in the striatum as markers. At 0.5 month after MPTP intoxication (80 mg/kg, i.p.), we observed comparable decreases of 83% in DA uptake, 83.3% in TH fiber density, and 74% in the number of TH-IR neurons compared to age-matched saline-treated animals. From 5 months onwards, both DA uptake and striatal TH fiber density increased significantly (50% and 34.9% at 5 months, 65% and 67.4% at 7 months, respectively) in comparison with age-matched saline-treated animals, although the number of TH-IR neurons remained stable (73% of degeneration at 7 months). These results indicate clearly that spontaneous long-term compensatory dopaminergic sprouting is a phenomenon that is not restricted to situations of partial nigral degeneration but can, on the contrary, constitute a response even to severe stable MPTP-induced nigral degeneration.