Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age.
Identifieur interne : 000307 ( Pmc/Checkpoint ); précédent : 000306; suivant : 000308Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age.
Auteurs : M Bannon ; M Poosch ; Y. Xia ; D Goebel ; B. Cassin ; G. KapatosSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 1992.
Abstract
The dopamine transporter is the primary means of inactivating synaptic dopamine as well as a major site of action for psychostimulants (such as cocaine and amphetamine) and for neurotoxins that induce parkinsonism. In the present study, a human dopamine transporter partial cDNA clone obtained by polymerase chain reaction exhibited 87% and 89% identity at the nucleic acid and amino acid levels, respectively, with transmembrane domains 3-5 of the rat homolog. This clone was used to quantitate human dopamine transporter mRNA by nuclease protection assay. The postmortem content of dopamine transporter mRNA in the substantia nigrae of 18- to 57-yr-old subjects was relatively constant, while in subjects greater than 57 yr old, a precipitous (greater than 95%) decline in substantia nigra dopamine transporter mRNA was evident. In contrast, tyrosine hydroxylase mRNA in the same samples declined in a linear manner with increasing age. In situ hybridization experiments confirmed the profound loss of dopamine transporter gene expression in melanin-positive (presumptive dopamine) nigral neurons. These data may begin to shed light on compensatory changes occurring in human dopamine neurons during normal aging.
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PubMed: 1353885
PubMed Central: 49652
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<author><name sortKey="Bannon, M J" sort="Bannon, M J" uniqKey="Bannon M" first="M" last="Bannon">M Bannon</name>
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<author><name sortKey="Poosch, M S" sort="Poosch, M S" uniqKey="Poosch M" first="M" last="Poosch">M Poosch</name>
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<author><name sortKey="Xia, Y" sort="Xia, Y" uniqKey="Xia Y" first="Y" last="Xia">Y. Xia</name>
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<author><name sortKey="Goebel, D J" sort="Goebel, D J" uniqKey="Goebel D" first="D" last="Goebel">D Goebel</name>
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<author><name sortKey="Cassin, B" sort="Cassin, B" uniqKey="Cassin B" first="B" last="Cassin">B. Cassin</name>
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<author><name sortKey="Kapatos, G" sort="Kapatos, G" uniqKey="Kapatos G" first="G" last="Kapatos">G. Kapatos</name>
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<author><name sortKey="Goebel, D J" sort="Goebel, D J" uniqKey="Goebel D" first="D" last="Goebel">D Goebel</name>
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<author><name sortKey="Cassin, B" sort="Cassin, B" uniqKey="Cassin B" first="B" last="Cassin">B. Cassin</name>
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<author><name sortKey="Kapatos, G" sort="Kapatos, G" uniqKey="Kapatos G" first="G" last="Kapatos">G. Kapatos</name>
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<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
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<front><div type="abstract" xml:lang="en"><p>The dopamine transporter is the primary means of inactivating synaptic dopamine as well as a major site of action for psychostimulants (such as cocaine and amphetamine) and for neurotoxins that induce parkinsonism. In the present study, a human dopamine transporter partial cDNA clone obtained by polymerase chain reaction exhibited 87% and 89% identity at the nucleic acid and amino acid levels, respectively, with transmembrane domains 3-5 of the rat homolog. This clone was used to quantitate human dopamine transporter mRNA by nuclease protection assay. The postmortem content of dopamine transporter mRNA in the substantia nigrae of 18- to 57-yr-old subjects was relatively constant, while in subjects greater than 57 yr old, a precipitous (greater than 95%) decline in substantia nigra dopamine transporter mRNA was evident. In contrast, tyrosine hydroxylase mRNA in the same samples declined in a linear manner with increasing age. In situ hybridization experiments confirmed the profound loss of dopamine transporter gene expression in melanin-positive (presumptive dopamine) nigral neurons. These data may begin to shed light on compensatory changes occurring in human dopamine neurons during normal aging.</p>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id>
<journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title>
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<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
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<title-group><article-title>Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age.</article-title>
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<contrib-group><contrib contrib-type="author"><name><surname>Bannon</surname>
<given-names>M J</given-names>
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<contrib contrib-type="author"><name><surname>Poosch</surname>
<given-names>M S</given-names>
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<contrib contrib-type="author"><name><surname>Xia</surname>
<given-names>Y</given-names>
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<contrib contrib-type="author"><name><surname>Goebel</surname>
<given-names>D J</given-names>
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<contrib contrib-type="author"><name><surname>Cassin</surname>
<given-names>B</given-names>
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<contrib contrib-type="author"><name><surname>Kapatos</surname>
<given-names>G</given-names>
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<aff>Department of Psychiatry (Cellular and Clinical Neurobiology Program), Wayne State University School of Medicine, Detroit, MI.</aff>
<pub-date pub-type="ppub"><day>1</day>
<month>8</month>
<year>1992</year>
</pub-date>
<volume>89</volume>
<issue>15</issue>
<fpage>7095</fpage>
<lpage>7099</lpage>
<abstract><p>The dopamine transporter is the primary means of inactivating synaptic dopamine as well as a major site of action for psychostimulants (such as cocaine and amphetamine) and for neurotoxins that induce parkinsonism. In the present study, a human dopamine transporter partial cDNA clone obtained by polymerase chain reaction exhibited 87% and 89% identity at the nucleic acid and amino acid levels, respectively, with transmembrane domains 3-5 of the rat homolog. This clone was used to quantitate human dopamine transporter mRNA by nuclease protection assay. The postmortem content of dopamine transporter mRNA in the substantia nigrae of 18- to 57-yr-old subjects was relatively constant, while in subjects greater than 57 yr old, a precipitous (greater than 95%) decline in substantia nigra dopamine transporter mRNA was evident. In contrast, tyrosine hydroxylase mRNA in the same samples declined in a linear manner with increasing age. In situ hybridization experiments confirmed the profound loss of dopamine transporter gene expression in melanin-positive (presumptive dopamine) nigral neurons. These data may begin to shed light on compensatory changes occurring in human dopamine neurons during normal aging.</p>
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<name sortKey="Goebel, D J" sort="Goebel, D J" uniqKey="Goebel D" first="D" last="Goebel">D Goebel</name>
<name sortKey="Kapatos, G" sort="Kapatos, G" uniqKey="Kapatos G" first="G" last="Kapatos">G. Kapatos</name>
<name sortKey="Poosch, M S" sort="Poosch, M S" uniqKey="Poosch M" first="M" last="Poosch">M Poosch</name>
<name sortKey="Xia, Y" sort="Xia, Y" uniqKey="Xia Y" first="Y" last="Xia">Y. Xia</name>
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