Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter
Identifieur interne : 001F65 ( Istex/Curation ); précédent : 001F64; suivant : 001F66Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter
Auteurs : Mohamed Jaber [France] ; Brigitte Dumartin [France] ; Corinne Sagné [France] ; John W. Haycock [États-Unis] ; Christine Roubert [France] ; Bruno Giros [France] ; Bertrand Bloch [France] ; Marc G. Caron [États-Unis]Source :
- European Journal of Neuroscience [ 0953-816X ] ; 1999-10.
English descriptors
Abstract
Mice lacking the dopamine transporter (DAT) display biochemical and behavioural dopaminergic hyperactivity despite dramatic alteration in dopamine homeostasis. In order to determine the anatomical and functional integrity of the dopaminergic system, we examined the expression of tyrosine hydroxylase (TH), the rate‐limiting enzyme of dopamine synthesis as well as DOPA decarboxylase and vesicular monoamine transporter. TH‐positive neurons in the substantia nigra were only slightly decreased (–27.6 ± 4.5%), which can not account for the dramatic decreases in the levels of TH and dopamine that we previously observed in the striatum. TH mRNA levels were decreased by 25% in the ventral midbrain with no modification in the ratio of TH mRNA levels per cell. However, TH protein levels were decreased by 90% in the striatum and 35% in the ventral midbrain. In the striatum, many dopaminergic projections had no detectable TH, while few projections maintained regular labelling as demonstrated using electron microscopy. DOPA decarboxylase levels were not modified and vesicular transporter levels were decreased by only 28.7% which suggests that the loss of TH labelling in the striatum is not due to loss of TH projections. Interestingly, we also observed sporadic TH‐positive cell bodies using immunohistochemistry and in situ hybridization in the striatum of homozygote mice, and to some extent that of wild‐type animals, which raises interesting possibilities as to their potential contribution to the dopamine hyperactivity and volume transmission previously reported in these animals. In conjunction with our previous findings, these results highlight the complex regulatory mechanisms controlling TH expression at the level of mRNA, protein, activity and distribution. The paradoxical hyperdopaminergia in the DAT KO mice despite a marked decrease in TH and dopamine levels suggests a parallel to Parkinson’s disease implying that blockade of DAT may be beneficial in this condition.
Url:
DOI: 10.1046/j.1460-9568.1999.00764.x
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001F67
Links to Exploration step
ISTEX:FBACD03590BAA0397A1C178B5C29AA8E2C4E0472Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter</title>
<author><name sortKey="Jaber, Mohamed" sort="Jaber, Mohamed" uniqKey="Jaber M" first="Mohamed" last="Jaber">Mohamed Jaber</name>
<affiliation wicri:level="1"><mods:affiliation>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dumartin, Brigitte" sort="Dumartin, Brigitte" uniqKey="Dumartin B" first="Brigitte" last="Dumartin">Brigitte Dumartin</name>
<affiliation wicri:level="1"><mods:affiliation>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sagne, Corinne" sort="Sagne, Corinne" uniqKey="Sagne C" first="Corinne" last="Sagné">Corinne Sagné</name>
<affiliation wicri:level="1"><mods:affiliation>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haycock, John W" sort="Haycock, John W" uniqKey="Haycock J" first="John W." last="Haycock">John W. Haycock</name>
<affiliation wicri:level="1"><mods:affiliation>Louisiana State University, Dept. of Biochemistry and Molecular Biology, New Orleans, LA 70119, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Louisiana State University, Dept. of Biochemistry and Molecular Biology, New Orleans, LA 70119</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Roubert, Christine" sort="Roubert, Christine" uniqKey="Roubert C" first="Christine" last="Roubert">Christine Roubert</name>
<affiliation wicri:level="1"><mods:affiliation>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Giros, Bruno" sort="Giros, Bruno" uniqKey="Giros B" first="Bruno" last="Giros">Bruno Giros</name>
<affiliation wicri:level="1"><mods:affiliation>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bloch, Bertrand" sort="Bloch, Bertrand" uniqKey="Bloch B" first="Bertrand" last="Bloch">Bertrand Bloch</name>
<affiliation wicri:level="1"><mods:affiliation>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Caron, Marc G" sort="Caron, Marc G" uniqKey="Caron M" first="Marc G." last="Caron">Marc G. Caron</name>
<affiliation wicri:level="2"><mods:affiliation>Howard Hughes Medical Institute Laboratories, Departments of Cell Biology and Medicine, Duke University Medical Center, Durham, NC 27710 USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Howard Hughes Medical Institute Laboratories, Departments of Cell Biology and Medicine, Duke University Medical Center, Durham</wicri:cityArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:FBACD03590BAA0397A1C178B5C29AA8E2C4E0472</idno>
<date when="1999" year="1999">1999</date>
<idno type="doi">10.1046/j.1460-9568.1999.00764.x</idno>
<idno type="url">https://api.istex.fr/document/FBACD03590BAA0397A1C178B5C29AA8E2C4E0472/fulltext/pdf</idno>
<idno type="wicri:Area/Istex/Corpus">001F67</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001F67</idno>
<idno type="wicri:Area/Istex/Curation">001F65</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter</title>
<author><name sortKey="Jaber, Mohamed" sort="Jaber, Mohamed" uniqKey="Jaber M" first="Mohamed" last="Jaber">Mohamed Jaber</name>
<affiliation wicri:level="1"><mods:affiliation>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dumartin, Brigitte" sort="Dumartin, Brigitte" uniqKey="Dumartin B" first="Brigitte" last="Dumartin">Brigitte Dumartin</name>
<affiliation wicri:level="1"><mods:affiliation>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sagne, Corinne" sort="Sagne, Corinne" uniqKey="Sagne C" first="Corinne" last="Sagné">Corinne Sagné</name>
<affiliation wicri:level="1"><mods:affiliation>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haycock, John W" sort="Haycock, John W" uniqKey="Haycock J" first="John W." last="Haycock">John W. Haycock</name>
<affiliation wicri:level="1"><mods:affiliation>Louisiana State University, Dept. of Biochemistry and Molecular Biology, New Orleans, LA 70119, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Louisiana State University, Dept. of Biochemistry and Molecular Biology, New Orleans, LA 70119</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Roubert, Christine" sort="Roubert, Christine" uniqKey="Roubert C" first="Christine" last="Roubert">Christine Roubert</name>
<affiliation wicri:level="1"><mods:affiliation>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Giros, Bruno" sort="Giros, Bruno" uniqKey="Giros B" first="Bruno" last="Giros">Bruno Giros</name>
<affiliation wicri:level="1"><mods:affiliation>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U‐288, 91 Boulevard de l’Hôpital, 75013 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bloch, Bertrand" sort="Bloch, Bertrand" uniqKey="Bloch B" first="Bertrand" last="Bloch">Bertrand Bloch</name>
<affiliation wicri:level="1"><mods:affiliation>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</mods:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS UMR 5541, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Caron, Marc G" sort="Caron, Marc G" uniqKey="Caron M" first="Marc G." last="Caron">Marc G. Caron</name>
<affiliation wicri:level="2"><mods:affiliation>Howard Hughes Medical Institute Laboratories, Departments of Cell Biology and Medicine, Duke University Medical Center, Durham, NC 27710 USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Howard Hughes Medical Institute Laboratories, Departments of Cell Biology and Medicine, Duke University Medical Center, Durham</wicri:cityArea>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">European Journal of Neuroscience</title>
<idno type="ISSN">0953-816X</idno>
<idno type="eISSN">1460-9568</idno>
<imprint><publisher>Blackwell Science Ltd</publisher>
<pubPlace>Oxford, UK</pubPlace>
<date type="published" when="1999-10">1999-10</date>
<biblScope unit="volume">11</biblScope>
<biblScope unit="issue">10</biblScope>
<biblScope unit="page" from="3499">3499</biblScope>
<biblScope unit="page" to="3511">3511</biblScope>
</imprint>
<idno type="ISSN">0953-816X</idno>
</series>
<idno type="istex">FBACD03590BAA0397A1C178B5C29AA8E2C4E0472</idno>
<idno type="DOI">10.1046/j.1460-9568.1999.00764.x</idno>
<idno type="ArticleID">EJN764</idno>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0953-816X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>DOPA decarboxylase</term>
<term>immunohistochemistry</term>
<term>knock‐out</term>
<term>vesicular monoamines transporter</term>
</keywords>
</textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Mice lacking the dopamine transporter (DAT) display biochemical and behavioural dopaminergic hyperactivity despite dramatic alteration in dopamine homeostasis. In order to determine the anatomical and functional integrity of the dopaminergic system, we examined the expression of tyrosine hydroxylase (TH), the rate‐limiting enzyme of dopamine synthesis as well as DOPA decarboxylase and vesicular monoamine transporter. TH‐positive neurons in the substantia nigra were only slightly decreased (–27.6 ± 4.5%), which can not account for the dramatic decreases in the levels of TH and dopamine that we previously observed in the striatum. TH mRNA levels were decreased by 25% in the ventral midbrain with no modification in the ratio of TH mRNA levels per cell. However, TH protein levels were decreased by 90% in the striatum and 35% in the ventral midbrain. In the striatum, many dopaminergic projections had no detectable TH, while few projections maintained regular labelling as demonstrated using electron microscopy. DOPA decarboxylase levels were not modified and vesicular transporter levels were decreased by only 28.7% which suggests that the loss of TH labelling in the striatum is not due to loss of TH projections. Interestingly, we also observed sporadic TH‐positive cell bodies using immunohistochemistry and in situ hybridization in the striatum of homozygote mice, and to some extent that of wild‐type animals, which raises interesting possibilities as to their potential contribution to the dopamine hyperactivity and volume transmission previously reported in these animals. In conjunction with our previous findings, these results highlight the complex regulatory mechanisms controlling TH expression at the level of mRNA, protein, activity and distribution. The paradoxical hyperdopaminergia in the DAT KO mice despite a marked decrease in TH and dopamine levels suggests a parallel to Parkinson’s disease implying that blockade of DAT may be beneficial in this condition.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001F65 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 001F65 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonFranceV1 |flux= Istex |étape= Curation |type= RBID |clé= ISTEX:FBACD03590BAA0397A1C178B5C29AA8E2C4E0472 |texte= Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter }}
![]() | This area was generated with Dilib version V0.6.29. | ![]() |