Zinc-induced apoptosis in substantia nigra of rat brain: neuroprotection by vitamin D3

Free Radical Biology & Medicine
Anya Maan-Yuh LinC H J Yang

Abstract

Accumulation of transition metals has been suggested to be responsible for the deteriorated nigrostriatal dopaminergic system in Parkinson's patients. In the present study, the mechanism underlying the zinc-induced neurotoxicity was investigated in the nigrostriatal dopaminergic system in vivo. Our 6-methoxy-8-paratoluene sulfonamide quinoline fluorescence study showed zinc translocation in the infused nigral cells after intranigral infusion of zinc. Furthermore, lipid peroxidation in the zinc-infused substantia nigra was consistently elevated 4 h to 7 d after the infusion. At the same time, an abrupt increase in cytosolic cytochrome c content in the infused substantia nigra was observed 4 h after zinc infusion and gradually decreased to basal levels 7 d after infusion. Both TUNEL-positive neurons and DNA fragmentation, indicatives of apoptosis, were detected in the zinc-infused substantia nigra. Furthermore, striatal dopamine content was reduced 7 d after the infusion. In attempt to prevent zinc-induced neurotoxicity, vitamin D3 was systemically administered. Zinc-induced increases in lipid peroxidation and cytosolic cytochrome c in the infused substantia nigra were prevented by this treatment. Moreover, zinc-induced reduction...Continue Reading

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