Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease.
Identifieur interne : 001865 ( PubMed/Corpus ); précédent : 001864; suivant : 001866Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease.
Auteurs : E. Hirsch ; A M Graybiel ; Y A AgidSource :
- Nature [ 0028-0836 ] ; 1988.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-Methyl-4-phenylpyridinium, Acetylcholinesterase (analysis), Dopamine, Humans, Melanins (analysis), Nerve Degeneration, Neurons (analysis), Parkinson Disease (pathology), Pyridines (analysis), Pyridinium Compounds (analysis), Tyrosine 3-Monooxygenase (analysis).
- MESH :
- chemical , analysis : Acetylcholinesterase, Melanins, Pyridines, Pyridinium Compounds, Tyrosine 3-Monooxygenase.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-Methyl-4-phenylpyridinium, Dopamine.
- analysis : Neurons.
- pathology : Parkinson Disease.
- Humans, Nerve Degeneration.
Abstract
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.
DOI: 10.1038/334345a0
PubMed: 2899295
Links to Exploration step
pubmed:2899295Le document en format XML
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Hirsch</name><affiliation><nlm:affiliation>INSERM U289, Laboratoire de Médecine Experimentale, Hôpital de la Salpêtrière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Graybiel, A M" sort="Graybiel, A M" uniqKey="Graybiel A" first="A M" last="Graybiel">A M Graybiel</name></author><author><name sortKey="Agid, Y A" sort="Agid, Y A" uniqKey="Agid Y" first="Y A" last="Agid">Y A Agid</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1988">1988</date><idno type="RBID">pubmed:2899295</idno><idno type="pmid">2899295</idno><idno type="doi">10.1038/334345a0</idno><idno type="wicri:Area/PubMed/Corpus">001865</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001865</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease.</title><author><name sortKey="Hirsch, E" sort="Hirsch, E" uniqKey="Hirsch E" first="E" last="Hirsch">E. Hirsch</name><affiliation><nlm:affiliation>INSERM U289, Laboratoire de Médecine Experimentale, Hôpital de la Salpêtrière, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Graybiel, A M" sort="Graybiel, A M" uniqKey="Graybiel A" first="A M" last="Graybiel">A M Graybiel</name></author><author><name sortKey="Agid, Y A" sort="Agid, Y A" uniqKey="Agid Y" first="Y A" last="Agid">Y A Agid</name></author></analytic><series><title level="j">Nature</title><idno type="ISSN">0028-0836</idno><imprint><date when="1988" type="published">1988</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>1-Methyl-4-phenylpyridinium</term><term>Acetylcholinesterase (analysis)</term><term>Dopamine</term><term>Humans</term><term>Melanins (analysis)</term><term>Nerve Degeneration</term><term>Neurons (analysis)</term><term>Parkinson Disease (pathology)</term><term>Pyridines (analysis)</term><term>Pyridinium Compounds (analysis)</term><term>Tyrosine 3-Monooxygenase (analysis)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Acetylcholinesterase</term><term>Melanins</term><term>Pyridines</term><term>Pyridinium Compounds</term><term>Tyrosine 3-Monooxygenase</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>1-Methyl-4-phenylpyridinium</term><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="analysis" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Nerve Degeneration</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">2899295</PMID><DateCreated><Year>1988</Year><Month>08</Month><Day>25</Day></DateCreated><DateCompleted><Year>1988</Year><Month>08</Month><Day>25</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0028-0836</ISSN><JournalIssue CitedMedium="Print"><Volume>334</Volume><Issue>6180</Issue><PubDate><Year>1988</Year><Month>Jul</Month><Day>28</Day></PubDate></JournalIssue><Title>Nature</Title><ISOAbbreviation>Nature</ISOAbbreviation></Journal><ArticleTitle>Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>345-8</MedlinePgn></Pagination><Abstract><AbstractText>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. 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