The effect of MPTP on uridine uptake in murine nerve cells

Abstract

Sixty, 3-month-old, male Theiler mice were injected with 1 mg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) each i.p. Six groups of 5 animals each were then injected with 0.25 mCi [5-H 3]uridine i.v. at intervals of 6 h, 1,2,5,7 and 9 weeks after MPTP injection and each group was killed 1 h after uridine injection. Microautoradiograms were performed and the grain number determined in nerve cell nuclei in the striatum, substantia nigra and cerebral cortex. An initial increase in uridine uptake was found in substantia nigra, followed by a decrease during the following 9 weeks. A decrease in uptake occurred in the striatum from weeks 5–9, but without any initial increase. An increase in uptake was observed in the cortex 2 weeks after MPTP injection. Thus, in mice, a single injection of MPTP has a significantly prolonged effect upon the basic metabolic process (RNA synthesis) in substantia nigra and striatum. Selegiline, which causes a significant decrease in uridine uptake, also protects nerve cells from the effect of MPTP. The amoutn of dopamine in striatum and substantia nigra following MPTP did not change significantly during the 9 weeks. However, the amount of dihydroxyphenylalanine (DOPA) increased in both these areas during this period.