INDUCTION BY 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE OF LIPID-PEROXIDATION INVIVO IN VITAMIN-E DEFICIENT MICE

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is neurotoxic to dopaminergic neurons in the midbrain and their projections into the striatum [I], It has been speculated that the mechanism of dopaminergic neurotoxicity involves at least two potential components: mitochondrial damage and oxidative stress. There is no question that MPTP is a mitochondrial toxin in vivo [2]. It is aiso widely accepted that MPTP induces oxidative stress in the lung in vivo [3,4], What is in question is which of these mechanisms might predominate in the neurotoxicity of MPTP. MPTP has been shown not to induce lipid peroxidation in vivo in the striatui [5]. Since lipid peroxidation may be a component of the toxicity of some oxidative stress-inducing agents, the lack of lipid peroxidation with MPTP might argue against oxidative stress as part of the neurotoxic mechanism. This study was performed to reexamine the induction of lipid peroxidation by MPTP, as measured by conjugated diene formation, in various brain regions as well as the striatum, In addition, vitamin E deficient mice were used since they are known to be more susceptible to oxidative stress than normal mice [6]. © 1989.