MPTP decreases MT-I mRNA in mouse striatum.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug that induces parkinsonism in humans and non-human primates. Free radicals are thought to be involved in its mechanism of action. Recently, metallothionein has been proposed to play a role as a scavenger of free radicals. In the present work, we studied the effect of MPTP neurotoxicity on brain metallothionein-I (MT-I) mRNA expression. Male C-57 black mice were treated with MPTP (30 mg/kg, i.p., daily) for 3 or 5 days. All animals were killed by cervical dislocation 7 days after the last MPTP dose. The brains were removed quickly and immediately frozen, and quantitative in situ hybridization was performed using MT-I cDNA probe. MT-I mRNA content in striatum, a region which is known to be highly predisposed and sensitive to MPTP-induced oxidative stress, decreased by 30% (3 days) and 39% (5 days) respectively, after the last MPTP administration. These results suggest that MT-I gene expression is decreased in MPTP neurotoxicity. It is suggested that the reduction of MT, an anti-oxidant and a free radical scavenger, in the striatum by MPTP enables the neurotoxin to exert maximal oxidative damage to the striatum.
Rojas
P
P
Laboratory of Neurotoxicology, Instituto Nacional de Neurología y Neurocirugía, México City, México.
Rojas-Castañeda
J
J
Vigueras
R M
RM
Habeebu
S S
SS
Rojas
C
C
Ríos
C
C
Ebadi
M
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D020267:MPTP Poisoning / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008668:Metallothionein / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D019287:Zinc Sulfate / Q000494:pharmacology
D016166:Free Radical Scavengers; D012333:RNA, Messenger; D019287:Zinc Sulfate; D008668:Metallothionein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine