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Tyrosine hydroxylase and dopamine transporter expression in residual dopaminergic neurons: Potential contributors to spontaneous recovery from experimental Parkinsonism

Identifieur interne : 001F28 ( Main/Corpus ); précédent : 001F27; suivant : 001F29

Tyrosine hydroxylase and dopamine transporter expression in residual dopaminergic neurons: Potential contributors to spontaneous recovery from experimental Parkinsonism

Auteurs : David S. Rothblat ; J. A. Schroeder ; J. S. Schneider

Source :

RBID : ISTEX:39FDE9D7EDB3F1ABD49C479BCA0373095E6C2CCB

English descriptors

Abstract

1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahyrdropyridine (MPTP)‐exposed cats develop severe Parkinsonism that spontaneously resolves in 4–6 weeks. The present study examined the extent to which compensatory changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) gene and protein expression may underlie this behavioral recovery. In normal cats, TH and DAT protein levels were higher in the dorsal vs. ventral striatum. Expression of DAT and TH mRNA was higher in substantia nigra pars compacta (SNc) than in the ventral tegmental area (VTA). In symptomatic parkinsonian animals, DAT and TH protein levels were significantly decreased in all striatal areas studied. TH and DAT mRNA expression in residual SNc neurons were decreased a mean 32% and 38%, respectively. DAT gene expression in residual VTA neurons in symptomatic animals was decreased 30% whereas TH gene expression was unaffected. In spontaneously recovered cats, TH protein levels were significantly higher than the levels in symptomatic cats only in the ventral striatum, whereas no increase in DAT protein levels were observed in any striatal area. Residual neurons in most ventral mesencephalic regions of recovered cats had increased TH mRNA expression but not increased DAT gene expression, compared with symptomatic animals. Thus, increased TH protein and mRNA and suppression of DAT protein and mRNA expression in the striatum and ventral mesencephalon were associated with functional recovery from MPTP‐induced parkinsonism. J. Neurosci. Res. 65:254–266, 2001. © 2001 Wiley‐Liss, Inc.

Url:
DOI: 10.1002/jnr.1149

Links to Exploration step

ISTEX:39FDE9D7EDB3F1ABD49C479BCA0373095E6C2CCB

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<namePart type="given">J.A.</namePart>
<namePart type="family">Schroeder</namePart>
<affiliation>Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania</affiliation>
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<name type="personal">
<namePart type="given">J.S.</namePart>
<namePart type="family">Schneider</namePart>
<affiliation>Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania</affiliation>
<description>Correspondence: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, 521 JAH, Philadelphia, PA 19107</description>
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<publisher>John Wiley & Sons, Inc.</publisher>
<place>
<placeTerm type="text">New York</placeTerm>
</place>
<dateIssued encoding="w3cdtf">2001-08-01</dateIssued>
<dateCaptured encoding="w3cdtf">2001-01-08</dateCaptured>
<dateValid encoding="w3cdtf">2001-03-30</dateValid>
<copyrightDate encoding="w3cdtf">2001</copyrightDate>
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<languageTerm type="code" authority="rfc3066">en</languageTerm>
<languageTerm type="code" authority="iso639-2b">eng</languageTerm>
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<extent unit="words">8290</extent>
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<abstract lang="en">1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahyrdropyridine (MPTP)‐exposed cats develop severe Parkinsonism that spontaneously resolves in 4–6 weeks. The present study examined the extent to which compensatory changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) gene and protein expression may underlie this behavioral recovery. In normal cats, TH and DAT protein levels were higher in the dorsal vs. ventral striatum. Expression of DAT and TH mRNA was higher in substantia nigra pars compacta (SNc) than in the ventral tegmental area (VTA). In symptomatic parkinsonian animals, DAT and TH protein levels were significantly decreased in all striatal areas studied. TH and DAT mRNA expression in residual SNc neurons were decreased a mean 32% and 38%, respectively. DAT gene expression in residual VTA neurons in symptomatic animals was decreased 30% whereas TH gene expression was unaffected. In spontaneously recovered cats, TH protein levels were significantly higher than the levels in symptomatic cats only in the ventral striatum, whereas no increase in DAT protein levels were observed in any striatal area. Residual neurons in most ventral mesencephalic regions of recovered cats had increased TH mRNA expression but not increased DAT gene expression, compared with symptomatic animals. Thus, increased TH protein and mRNA and suppression of DAT protein and mRNA expression in the striatum and ventral mesencephalon were associated with functional recovery from MPTP‐induced parkinsonism. J. Neurosci. Res. 65:254–266, 2001. © 2001 Wiley‐Liss, Inc.</abstract>
<note type="funding">NIH - No. NS 23980; </note>
<subject lang="en">
<genre>Keywords</genre>
<topic>striatum</topic>
<topic>substantia nigra</topic>
<topic>ventral tegmental area</topic>
<topic>dopamine</topic>
<topic>retrorubral area</topic>
</subject>
<relatedItem type="host">
<titleInfo>
<title>Journal of Neuroscience Research</title>
</titleInfo>
<titleInfo type="abbreviated">
<title>J. Neurosci. Res.</title>
</titleInfo>
<genre type="Journal">journal</genre>
<subject>
<genre>article category</genre>
<topic>Article</topic>
</subject>
<identifier type="ISSN">0360-4012</identifier>
<identifier type="eISSN">1097-4547</identifier>
<identifier type="DOI">10.1002/(ISSN)1097-4547</identifier>
<identifier type="PublisherID">JNR</identifier>
<part>
<date>2001</date>
<detail type="volume">
<caption>vol.</caption>
<number>65</number>
</detail>
<detail type="issue">
<caption>no.</caption>
<number>3</number>
</detail>
<extent unit="pages">
<start>254</start>
<end>266</end>
<total>13</total>
</extent>
</part>
</relatedItem>
<identifier type="istex">39FDE9D7EDB3F1ABD49C479BCA0373095E6C2CCB</identifier>
<identifier type="DOI">10.1002/jnr.1149</identifier>
<identifier type="ArticleID">JNR1149</identifier>
<accessCondition type="use and reproduction" contentType="copyright">Copyright © 2001 Wiley‐Liss, Inc.</accessCondition>
<recordInfo>
<recordContentSource>WILEY</recordContentSource>
<recordOrigin>John Wiley & Sons, Inc.</recordOrigin>
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<serie></serie>
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