Functional Alterations in Striatal Cholinergic and Striato-Nigral Gaba-Ergic Neurons Following 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Administration
It has been well documented that systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) to humans, monkeys, and mice induces various motor disturbances resembling Parkinson’s disease due to the destruction of nigro-striatal dopaminergic neurons.1–3 Concerning the mechanism of the neurotoxicity, it is considered that the 1-methyl-4-phenylpyridinium ion(MPP+), which is converted from MPTP by monoamine oxidase type B in cerebral glial cells and accumulates in the cell body and/or terminals of the nigro-striatal dopaminergic neuron4,5, induces a significant decrement of dopamine content associated with the inhibition of tyrosine hydroxylase in the striatum,6,7 a significant loss of nerve cells due to the binding to neuromelanin,8,9 and the inhibition of NADH-ubiquinone oxidoreductase10 in the substantia nigra.
KeywordsTyrosine Hydroxylase Substantia Nigra Dopamine Content Gaba Content MPTP Administration
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