Selenium deficiency potentiates methamphetamine-induced nigral neuronal loss; comparison with MPTP model.
The present study was designed to understand the role of an antioxidant, selenium (Se) on methamphetamine (MA)-induced dopaminergic cell damage in the substantia nigra (SN). Male C57BL/6J mice were fed either selenium-deficient (<0.01 ppm Se) or selenium-replete (0.2 ppm Se) diet for 90 days. Se-deficiency potentiates MA-induced reductions of tyrosine hydroxylase-like immunoreactivity (TH-IR), dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in the SN. These dopaminergic toxicities were comparable to that induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). By contrast, Se-repletion significantly blocked dopaminergic toxicity after MA treatments. These results suggest that Se-deficient MA-treated mouse is a relevant model of Parkinsonism, and that optimal level of Se plays a crucial role in preventing nigral dopaminergic toxicity induced by MA. However, different mechanisms in the thermoregulation mediated by MA or MPTP remain to be further determined.
Kim
H
H
Section of Pharmacology and Toxicology, Department of Pharmacy, College of Pharmacy, Kangwon National University, Korea Institute of Drug Abuse, Chunchon, South Korea. kimhc@cc.kangwon.ac.kr
Jhoo
W
W
Shin
E
E
Bing
G
G
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004032:Diet; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D012643:Selenium / Q000172:deficiency*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000975:Antioxidants; D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D012643:Selenium; D004298:Dopamine; D006719:Homovanillic Acid