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 wo
rk, 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 dislo
cation 7 days after the last MPTP dose. The brains were removed quickly and
immediately frozen, and quantitative in situ hybridization was performed u
sing MT-I cDNA probe. MT-I mRNA content in striatum, a region which is know
n to be highly predisposed and sensitive to MPTP-induced oxidative stress,
decreased by 30% (3 days) and 39% (5 days) respectively, after the last MPT
P administration. These results suggest that MT-I gene expression is decrea
sed in MPTP neurotoxicity. it is suggested that the reduction of MT, an ant
i-oxidant and a free radical scavenger, in the striatum by MPTP enables the
neurotoxin to exert maximal oxidative damage to the striatum.