Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease.
In idiopathic Parkinson's disease massive cell death occurs in the dopamine-containing substantia nigra. A link between the vulnerability of nigral neurons and the prominent pigmentation of the substantia nigra, though long suspected, has not been proved. This possibility is supported by evidence that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite MPP+, the latter of which causes destruction of nigral neurons, bind to neuromelanin. We have directly tested this hypothesis by a quantitative analysis of neuromelanin-pigmented neurons in control and parkinsonian midbrains. The findings demonstrate first that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neuromelanin-pigmented neurons they contain. Second, the estimated cell loss in these cell groups in Parkinson's disease is directly correlated (r = 0.97, P = 0.0057) with the percentage of neuromelanin-pigmented neurons normally present in them. Third, within each cell group in the Parkinson's brains, there is greater relative sparing of non-pigmented than of neuromelanin-pigmented neurons. This evidence suggests a selective vulnerability of the neuromelanin-pigmented subpopulation of dopamine-containing mesencephalic neurons in Parkinson's disease.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000110:Acetylcholinesterase / Q000032:analysis; D004298:Dopamine; D006801:Humans; D008543:Melanins / Q000032:analysis*; D009410:Nerve Degeneration; D009474:Neurons / Q000032:analysis*; D010300:Parkinson Disease / Q000473:pathology*; D011725:Pyridines / Q000032:analysis; D011726:Pyridinium Compounds / Q000032:analysis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D008543:Melanins; D011725:Pyridines; D011726:Pyridinium Compounds; C014121:neuromelanin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine