Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy
Identifieur interne : 001E80 ( Istex/Corpus ); précédent : 001E79; suivant : 001E81Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy
Auteurs : Chaodong Kastner ; M. T. Herrero ; E. C. Hirsch ; J. Guillen ; M. R. Luquin ; F. Javoy-Agid ; J. A. Obeso ; Y. AgidSource :
- Annals of Neurology [ 0364-5134 ] ; 1994-08.
Abstract
Parkinson's disease is characterized by the degeneration of melanized dopaminergic neurons of the substantia nigra. The functional capacity of the surviving dopaminergic neurons is affected, as suggested by the subnormal levels of tyrosine hydroxylase messenger RNA and protein found in the remaining cells. The reduced expression of tyrosine hydroxylase may be due to either the evolving neurodegenerative process or its downregulation, possibly secondary to chronic levodopa treatment. The cellular content of tyrosine hydroxylase was determined in the mesencephalon from 16 Macaca fascicularis monkeys, using a semiquantitative immunocytochemical method. Thirteen monkeys were rendered parkinsonian by weekly intravenous injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) for 2 (subacute treatment) or 20 (chronic treatment) weeks. Three of the monkeys received levodopa and 3 others received GM1 ganglioside. The loss of dopaminergic neurons in the mesencephalon of the MPTP‐intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance. After both subacute and chronic treatment, the cellular content of tyrosine hydroxylase was reduced by 40% in the surviving neurons of the lesioned substantia nigra, but by less in the other mesencephalic dopaminergic regions. Neuronal survival and tyrosine hydroxylase content in monkeys that had received levodopa were not significantly different. The cellular content of tyrosine hydroxylase was increased in the substantia nigra of the monkeys that received GM1 ganglioside injections. The results show that the decreased expression of tyrosine hydroxylase found in nigral dopaminergic neurons after partial degeneration of the mesostriatal dopaminergic system is not influenced by levodopa treatment and is partially reversed by GM1 ganglioside administration.
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DOI: 10.1002/ana.410360213
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Herrero</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E. C." last="Hirsch">E. C. Hirsch</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Guillen, J" sort="Guillen, J" uniqKey="Guillen J" first="J." last="Guillen">J. Guillen</name><affiliation><mods:affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Luquin, M R" sort="Luquin, M R" uniqKey="Luquin M" first="M. R." last="Luquin">M. R. Luquin</name><affiliation><mods:affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Javoy Gid, F" sort="Javoy Gid, F" uniqKey="Javoy Gid F" first="F." last="Javoy-Agid">F. Javoy-Agid</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Obeso, J A" sort="Obeso, J A" uniqKey="Obeso J" first="J. A." last="Obeso">J. A. Obeso</name><affiliation><mods:affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Y. Agid</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:0054A336EE537968F5CE09F452C10BBA0BC1A4D9</idno><date when="1994" year="1994">1994</date><idno type="doi">10.1002/ana.410360213</idno><idno type="url">https://api.istex.fr/document/0054A336EE537968F5CE09F452C10BBA0BC1A4D9/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001E80</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001E80</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy</title><author><name sortKey="Kastner, Chaodong" sort="Kastner, Chaodong" uniqKey="Kastner C" first="Chaodong" last="Kastner">Chaodong Kastner</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Herrero, M T" sort="Herrero, M T" uniqKey="Herrero M" first="M. T." last="Herrero">M. T. Herrero</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E. C." last="Hirsch">E. C. Hirsch</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Guillen, J" sort="Guillen, J" uniqKey="Guillen J" first="J." last="Guillen">J. Guillen</name><affiliation><mods:affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Luquin, M R" sort="Luquin, M R" uniqKey="Luquin M" first="M. R." last="Luquin">M. R. Luquin</name><affiliation><mods:affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Javoy Gid, F" sort="Javoy Gid, F" uniqKey="Javoy Gid F" first="F." last="Javoy-Agid">F. Javoy-Agid</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Obeso, J A" sort="Obeso, J A" uniqKey="Obeso J" first="J. A." last="Obeso">J. A. Obeso</name><affiliation><mods:affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Y. Agid</name><affiliation><mods:affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="sub">Official Journal of the American Neurological Association and the Child Neurology Society</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="1994-08">1994-08</date><biblScope unit="volume">36</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="206">206</biblScope><biblScope unit="page" to="214">214</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">0054A336EE537968F5CE09F452C10BBA0BC1A4D9</idno><idno type="DOI">10.1002/ana.410360213</idno><idno type="ArticleID">ANA410360213</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease is characterized by the degeneration of melanized dopaminergic neurons of the substantia nigra. The functional capacity of the surviving dopaminergic neurons is affected, as suggested by the subnormal levels of tyrosine hydroxylase messenger RNA and protein found in the remaining cells. The reduced expression of tyrosine hydroxylase may be due to either the evolving neurodegenerative process or its downregulation, possibly secondary to chronic levodopa treatment. The cellular content of tyrosine hydroxylase was determined in the mesencephalon from 16 Macaca fascicularis monkeys, using a semiquantitative immunocytochemical method. Thirteen monkeys were rendered parkinsonian by weekly intravenous injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) for 2 (subacute treatment) or 20 (chronic treatment) weeks. Three of the monkeys received levodopa and 3 others received GM1 ganglioside. The loss of dopaminergic neurons in the mesencephalon of the MPTP‐intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance. After both subacute and chronic treatment, the cellular content of tyrosine hydroxylase was reduced by 40% in the surviving neurons of the lesioned substantia nigra, but by less in the other mesencephalic dopaminergic regions. Neuronal survival and tyrosine hydroxylase content in monkeys that had received levodopa were not significantly different. The cellular content of tyrosine hydroxylase was increased in the substantia nigra of the monkeys that received GM1 ganglioside injections. The results show that the decreased expression of tyrosine hydroxylase found in nigral dopaminergic neurons after partial degeneration of the mesostriatal dopaminergic system is not influenced by levodopa treatment and is partially reversed by GM1 ganglioside administration.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Dr. Kastner PhD</name><affiliations><json:string>INSERM U289, Hôpital de la Salpêtrière, Paris, France</json:string><json:string>INSERM U289, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France</json:string></affiliations></json:item><json:item><name>M. T. Herrero MD, PhD</name><affiliations><json:string>INSERM U289, Hôpital de la Salpêtrière, Paris, France</json:string><json:string>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</json:string></affiliations></json:item><json:item><name>E. C. Hirsch PhD</name><affiliations><json:string>INSERM U289, Hôpital de la Salpêtrière, Paris, France</json:string></affiliations></json:item><json:item><name>J. Guillen PhD</name><affiliations><json:string>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</json:string></affiliations></json:item><json:item><name>M. R. Luquin MD, PhD</name><affiliations><json:string>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</json:string></affiliations></json:item><json:item><name>F. Javoy‐Agid PhD</name><affiliations><json:string>INSERM U289, Hôpital de la Salpêtrière, Paris, France</json:string></affiliations></json:item><json:item><name>J. A. Obeso MD, PhD</name><affiliations><json:string>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</json:string></affiliations></json:item><json:item><name>Y. Agid MD, PhD</name><affiliations><json:string>INSERM U289, Hôpital de la Salpêtrière, Paris, France</json:string></affiliations></json:item></author><articleId><json:string>ANA410360213</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Parkinson's disease is characterized by the degeneration of melanized dopaminergic neurons of the substantia nigra. The functional capacity of the surviving dopaminergic neurons is affected, as suggested by the subnormal levels of tyrosine hydroxylase messenger RNA and protein found in the remaining cells. The reduced expression of tyrosine hydroxylase may be due to either the evolving neurodegenerative process or its downregulation, possibly secondary to chronic levodopa treatment. The cellular content of tyrosine hydroxylase was determined in the mesencephalon from 16 Macaca fascicularis monkeys, using a semiquantitative immunocytochemical method. Thirteen monkeys were rendered parkinsonian by weekly intravenous injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) for 2 (subacute treatment) or 20 (chronic treatment) weeks. Three of the monkeys received levodopa and 3 others received GM1 ganglioside. The loss of dopaminergic neurons in the mesencephalon of the MPTP‐intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance. After both subacute and chronic treatment, the cellular content of tyrosine hydroxylase was reduced by 40% in the surviving neurons of the lesioned substantia nigra, but by less in the other mesencephalic dopaminergic regions. Neuronal survival and tyrosine hydroxylase content in monkeys that had received levodopa were not significantly different. The cellular content of tyrosine hydroxylase was increased in the substantia nigra of the monkeys that received GM1 ganglioside injections. The results show that the decreased expression of tyrosine hydroxylase found in nigral dopaminergic neurons after partial degeneration of the mesostriatal dopaminergic system is not influenced by levodopa treatment and is partially reversed by GM1 ganglioside administration.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>576 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1910</abstractCharCount><pdfWordCount>5215</pdfWordCount><pdfCharCount>33024</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>261</abstractWordCount></qualityIndicators><title>Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy</title><refBibs><json:item><author><json:item><name>O Hornykiewicz</name></json:item></author><host><volume>18</volume><pages><last>964</last><first>925</first></pages><author></author><title>Pharmacol Rev</title></host><title>Dopamine (3‐hydroxytyramine) and brain function</title></json:item><json:item><author><json:item><name>Y Agid</name></json:item><json:item><name>AM Graybiel</name></json:item><json:item><name>M Ruberg</name></json:item></author><host><volume>53</volume><pages><last>100</last><first>83</first></pages><author></author><title>Adv Neurol</title></host><title>The efficacy of levodopa declines in the course of Parkinson's disease: do nondopaminergic lesions play a role?</title></json:item><json:item><author><json:item><name>N Ogawa</name></json:item><json:item><name>R Edamatsu</name></json:item><json:item><name>K Mizukawa</name></json:item></author><host><volume>60</volume><pages><last>250</last><first>242</first></pages><author></author><title>Adv Neurol</title></host><title>Degeneration of dopaminergic neurons and free radicals. 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Specific effects of GM3 on tyrosine phosphorylation of the epidermal growth factor receptor</title></json:item><json:item><author><json:item><name>EJ Lewis</name></json:item><json:item><name>DM Chikaraishi</name></json:item></author><host><volume>7</volume><pages><last>3336</last><first>3332</first></pages><author></author><title>Mol Cell Biol</title></host><title>Regulated expression of the tyrosine hydroxylase gene by epidermal growth factor</title></json:item></refBibs><genre><json:string>article</json:string></genre><host><volume>36</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>9</total><last>214</last><first>206</first></pages><issn><json:string>0364-5134</json:string></issn><issue>2</issue><subject><json:item><value>Original Article</value></json:item></subject><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8249</json:string></eissn><title>Annals of Neurology</title><doi><json:string>10.1002/(ISSN)1531-8249</json:string></doi></host><categories><wos><json:string>science</json:string><json:string>neurosciences</json:string><json:string>clinical neurology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>neurology & neurosurgery</json:string></scienceMetrix></categories><publicationDate>1994</publicationDate><copyrightDate>1994</copyrightDate><doi><json:string>10.1002/ana.410360213</json:string></doi><id>0054A336EE537968F5CE09F452C10BBA0BC1A4D9</id><score>0.16474968</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/0054A336EE537968F5CE09F452C10BBA0BC1A4D9/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/0054A336EE537968F5CE09F452C10BBA0BC1A4D9/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/0054A336EE537968F5CE09F452C10BBA0BC1A4D9/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Copyright © 1994 American Neurological Association</p></availability><date>1994</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy</title><author xml:id="author-1"><persName><surname>Kastner</surname></persName><roleName type="degree">Dr.</roleName><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation><affiliation>INSERM U289, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France</affiliation></author><author xml:id="author-2"><persName><forename type="first">M. T.</forename><surname>Herrero</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation><affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</affiliation></author><author xml:id="author-3"><persName><forename type="first">E. C.</forename><surname>Hirsch</surname></persName><roleName type="degree">PhD</roleName><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation></author><author xml:id="author-4"><persName><forename type="first">J.</forename><surname>Guillen</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</affiliation></author><author xml:id="author-5"><persName><forename type="first">M. R.</forename><surname>Luquin</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</affiliation></author><author xml:id="author-6"><persName><forename type="first">F.</forename><surname>Javoy‐Agid</surname></persName><roleName type="degree">PhD</roleName><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">J. A.</forename><surname>Obeso</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</affiliation></author><author xml:id="author-8"><persName><forename type="first">Y.</forename><surname>Agid</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="sub">Official Journal of the American Neurological Association and the Child Neurology Society</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="1994-08"></date><biblScope unit="volume">36</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="206">206</biblScope><biblScope unit="page" to="214">214</biblScope></imprint></monogr><idno type="istex">0054A336EE537968F5CE09F452C10BBA0BC1A4D9</idno><idno type="DOI">10.1002/ana.410360213</idno><idno type="ArticleID">ANA410360213</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1994</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Parkinson's disease is characterized by the degeneration of melanized dopaminergic neurons of the substantia nigra. The functional capacity of the surviving dopaminergic neurons is affected, as suggested by the subnormal levels of tyrosine hydroxylase messenger RNA and protein found in the remaining cells. The reduced expression of tyrosine hydroxylase may be due to either the evolving neurodegenerative process or its downregulation, possibly secondary to chronic levodopa treatment. The cellular content of tyrosine hydroxylase was determined in the mesencephalon from 16 Macaca fascicularis monkeys, using a semiquantitative immunocytochemical method. Thirteen monkeys were rendered parkinsonian by weekly intravenous injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) for 2 (subacute treatment) or 20 (chronic treatment) weeks. Three of the monkeys received levodopa and 3 others received GM1 ganglioside. The loss of dopaminergic neurons in the mesencephalon of the MPTP‐intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance. After both subacute and chronic treatment, the cellular content of tyrosine hydroxylase was reduced by 40% in the surviving neurons of the lesioned substantia nigra, but by less in the other mesencephalic dopaminergic regions. Neuronal survival and tyrosine hydroxylase content in monkeys that had received levodopa were not significantly different. The cellular content of tyrosine hydroxylase was increased in the substantia nigra of the monkeys that received GM1 ganglioside injections. The results show that the decreased expression of tyrosine hydroxylase found in nigral dopaminergic neurons after partial degeneration of the mesostriatal dopaminergic system is not influenced by levodopa treatment and is partially reversed by GM1 ganglioside administration.</p></abstract><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Original Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1993-08-30">Received</change><change when="1994-01-20">Registration</change><change when="1994-08">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/0054A336EE537968F5CE09F452C10BBA0BC1A4D9/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8249</doi><issn type="print">0364-5134</issn><issn type="electronic">1531-8249</issn><idGroup><id type="product" value="ANA"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="ANNALS OF NEUROLOGY">Annals of Neurology</title><title type="subtitle">Official Journal of the American Neurological Association and the Child Neurology Society</title><title type="short">Ann Neurol.</title></titleGroup></publicationMeta><publicationMeta level="part" position="20"><doi origin="wiley" registered="yes">10.1002/ana.v36:2</doi><numberingGroup><numbering type="journalVolume" number="36">36</numbering><numbering type="journalIssue">2</numbering></numberingGroup><coverDate startDate="1994-08">August 1994</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="13" status="forIssue"><doi origin="wiley" registered="yes">10.1002/ana.410360213</doi><idGroup><id type="unit" value="ANA410360213"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 1994 American Neurological Association</copyright><eventGroup><event type="manuscriptReceived" date="1993-08-30"></event><event type="manuscriptRevised" date="1993-12-21"></event><event type="manuscriptAccepted" date="1994-01-20"></event><event type="firstOnline" date="2004-10-08"></event><event type="publishedOnlineFinalForm" date="2004-10-08"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.1 mode:FullText source:HeaderRef result:HeaderRef" date="2010-02-23"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-03"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">206</numbering><numbering type="pageLast">214</numbering></numberingGroup><correspondenceTo>INSERM U289, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA410360213.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="46"></count></countGroup><titleGroup><title type="main" xml:lang="en">Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy</title><title type="short" xml:lang="en">Tyrosine Hydroxylase in MPTP‐intoxicated Monkeys</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><honorifics>Dr.</honorifics><givenNames>A.</givenNames><familyName>Kastner</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>M. T.</givenNames><familyName>Herrero</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>E. C.</givenNames><familyName>Hirsch</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af2"><personName><givenNames>J.</givenNames><familyName>Guillen</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af2"><personName><givenNames>M. R.</givenNames><familyName>Luquin</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>F.</givenNames><familyName>Javoy‐Agid</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af2"><personName><givenNames>J. A.</givenNames><familyName>Obeso</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Y.</givenNames><familyName>Agid</familyName><degrees>MD, PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="FR" type="organization"><unparsedAffiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="ES" type="organization"><unparsedAffiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Parkinson's disease is characterized by the degeneration of melanized dopaminergic neurons of the substantia nigra. The functional capacity of the surviving dopaminergic neurons is affected, as suggested by the subnormal levels of tyrosine hydroxylase messenger RNA and protein found in the remaining cells. The reduced expression of tyrosine hydroxylase may be due to either the evolving neurodegenerative process or its downregulation, possibly secondary to chronic levodopa treatment. The cellular content of tyrosine hydroxylase was determined in the mesencephalon from 16 <i>Macaca fascicularis</i> monkeys, using a semiquantitative immunocytochemical method. Thirteen monkeys were rendered parkinsonian by weekly intravenous injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) for 2 (subacute treatment) or 20 (chronic treatment) weeks. Three of the monkeys received levodopa and 3 others received GM1 ganglioside. The loss of dopaminergic neurons in the mesencephalon of the MPTP‐intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance. After both subacute and chronic treatment, the cellular content of tyrosine hydroxylase was reduced by 40% in the surviving neurons of the lesioned substantia nigra, but by less in the other mesencephalic dopaminergic regions. Neuronal survival and tyrosine hydroxylase content in monkeys that had received levodopa were not significantly different. The cellular content of tyrosine hydroxylase was increased in the substantia nigra of the monkeys that received GM1 ganglioside injections. The results show that the decreased expression of tyrosine hydroxylase found in nigral dopaminergic neurons after partial degeneration of the mesostriatal dopaminergic system is not influenced by levodopa treatment and is partially reversed by GM1 ganglioside administration.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Tyrosine Hydroxylase in MPTP‐intoxicated Monkeys</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP–intoxicated monkeys: Effect of levodopa and GM1 ganglioside therapy</title></titleInfo><name type="personal"><namePart type="termsOfAddress">Dr.</namePart><namePart type="family">Kastner</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation><affiliation>INSERM U289, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M. T.</namePart><namePart type="family">Herrero</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation><affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E. C.</namePart><namePart type="family">Hirsch</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.</namePart><namePart type="family">Guillen</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M. R.</namePart><namePart type="family">Luquin</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F.</namePart><namePart type="family">Javoy‐Agid</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J. A.</namePart><namePart type="family">Obeso</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology and Experimental Neurology, CIFA, University of Navarre, Pamplona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Y.</namePart><namePart type="family">Agid</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>INSERM U289, Hôpital de la Salpêtrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">1994-08</dateIssued><dateCaptured encoding="w3cdtf">1993-08-30</dateCaptured><dateValid encoding="w3cdtf">1994-01-20</dateValid><copyrightDate encoding="w3cdtf">1994</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">3</extent><extent unit="tables">2</extent><extent unit="references">46</extent></physicalDescription><abstract lang="en">Parkinson's disease is characterized by the degeneration of melanized dopaminergic neurons of the substantia nigra. The functional capacity of the surviving dopaminergic neurons is affected, as suggested by the subnormal levels of tyrosine hydroxylase messenger RNA and protein found in the remaining cells. The reduced expression of tyrosine hydroxylase may be due to either the evolving neurodegenerative process or its downregulation, possibly secondary to chronic levodopa treatment. The cellular content of tyrosine hydroxylase was determined in the mesencephalon from 16 Macaca fascicularis monkeys, using a semiquantitative immunocytochemical method. Thirteen monkeys were rendered parkinsonian by weekly intravenous injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) for 2 (subacute treatment) or 20 (chronic treatment) weeks. Three of the monkeys received levodopa and 3 others received GM1 ganglioside. The loss of dopaminergic neurons in the mesencephalon of the MPTP‐intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance. After both subacute and chronic treatment, the cellular content of tyrosine hydroxylase was reduced by 40% in the surviving neurons of the lesioned substantia nigra, but by less in the other mesencephalic dopaminergic regions. Neuronal survival and tyrosine hydroxylase content in monkeys that had received levodopa were not significantly different. The cellular content of tyrosine hydroxylase was increased in the substantia nigra of the monkeys that received GM1 ganglioside injections. The results show that the decreased expression of tyrosine hydroxylase found in nigral dopaminergic neurons after partial degeneration of the mesostriatal dopaminergic system is not influenced by levodopa treatment and is partially reversed by GM1 ganglioside administration.</abstract><relatedItem type="host"><titleInfo><title>Annals of Neurology</title><subTitle>Official Journal of the American Neurological Association and the Child Neurology Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>1994</date><detail type="volume"><caption>vol.</caption><number>36</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>206</start><end>214</end><total>9</total></extent></part></relatedItem><identifier type="istex">0054A336EE537968F5CE09F452C10BBA0BC1A4D9</identifier><identifier type="DOI">10.1002/ana.410360213</identifier><identifier type="ArticleID">ANA410360213</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 1994 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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