Zinc-induced apoptosis in substantia nigra of rat brain: neuroprotection by vitamin D3.
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 in striatal dopamine content was attenuated after vitamin D3 treatment. Our in vivo data suggest that zinc-induced oxidative stress may result in apoptosis followed by reduced dopaminergic function in the nigrostriatal dopaminergic system. Furthermore, vitamin D3 prevented zinc-induced oxidative injuries in the rat brain.
Lin
Anya M Y
AM
Department of Medical Research and Education, Veterans General Hospital-Taipei, Taipei, Taiwan
Fan
S F
SF
Yang
D M
DM
Hsu
L L
LL
Yang
C H J
CH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002762:Cholecalciferol / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D045304:Cytochromes c / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation; D008297:Male; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D015032:Zinc / Q000494:pharmacology*
D018696:Neuroprotective Agents; D002762:Cholecalciferol; D045304:Cytochromes c; D015032:Zinc; D004298:Dopamine