A Progressive Ballooning of Myelinated, TH-Positive Axons is Produced by MPTP in the Dog
Systemic injections of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) produce selective degeneration of the dopaminergic neurons of the nigrostriatal pathway in some mammals such as dogs, monkeys, and humans but not others such as rats. The mechanism of MPTP’s actions has been studied by biochemical and pharmacological techniques which have found that MPTP’s toxicity requires its oxidation by glial MAO-B to l-methyl-4-phenylpyridinium (MPP+)1–3. Surprisingly, MPP+ is not selectively toxic to dopaminergic neurons but damages or kills most cells with which it comes into contact including hepatocytes and granule cells of the cerebellum4,5.
KeywordsAmyotrophic Lateral Sclerosis Substantia Nigra Dopaminergic Neuron Myelinated Axon Nigrostriatal Pathway
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