Effect of MPTP‐induced denervation on basal ganglia GABAB receptors: Correlation with dopamine concentrations and dopamine transporter
Identifieur interne : 003237 ( Main/Exploration ); précédent : 003236; suivant : 003238Effect of MPTP‐induced denervation on basal ganglia GABAB receptors: Correlation with dopamine concentrations and dopamine transporter
Auteurs : Frédéric Calon [Canada] ; Nadia Lavertu [Canada] ; Anne-Marie Lemieux [Canada] ; Marc Morissette [Canada] ; Martin Goulet [Canada] ; Richard Grondin [Canada] ; Pierre J. Blanchet [Canada] ; Paul J. Bédard [Canada] ; Thérèse Di Paolo [Canada]Source :
- Synapse [ 0887-4476 ] ; 2001-06-01.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Basal Ganglia (metabolism), Basal Ganglia (physiopathology), Benzoates (metabolism), Cocaine (analogs & derivatives), Cocaine (metabolism), Corpus Striatum (metabolism), Corpus Striatum (physiopathology), Disease Models, Animal, Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins, Dose-Response Relationship, Drug, Female, GABA, Macaca fascicularis, Male, Membrane Glycoproteins (metabolism), Membrane Transport Proteins (metabolism), Mice, Mice, Inbred C57BL, Nerve Tissue Proteins (metabolism), Organophosphorus Compounds (metabolism), Parkinson, Parkinsonian Disorders (chemically induced), Parkinsonian Disorders (metabolism), Parkinsonian Disorders (physiopathology), Protein Subunits (genetics), Protein Subunits (metabolism), RNA, Messenger (metabolism), Radioligand Assay, Receptors, GABA-B (genetics), Receptors, GABA-B (metabolism), Substantia Nigra (metabolism), Substantia Nigra (physiopathology), Subthalamic Nucleus (metabolism), Subthalamic Nucleus (physiopathology), autoradiography, dopamine, in situ hybridization, substantia nigra.
- MESH :
- chemical , analogs & derivatives : Cocaine.
- chemical , genetics : Protein Subunits, Receptors, GABA-B.
- chemical , metabolism : Benzoates, Cocaine, Dopamine, Membrane Glycoproteins, Membrane Transport Proteins, Nerve Tissue Proteins, Organophosphorus Compounds, Protein Subunits, RNA, Messenger, Receptors, GABA-B.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Dopamine Plasma Membrane Transport Proteins.
- chemically induced : Parkinsonian Disorders.
- metabolism : Basal Ganglia, Corpus Striatum, Parkinsonian Disorders, Substantia Nigra, Subthalamic Nucleus.
- physiopathology : Basal Ganglia, Corpus Striatum, Parkinsonian Disorders, Substantia Nigra, Subthalamic Nucleus.
- Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Macaca fascicularis, Male, Mice, Mice, Inbred C57BL, Radioligand Assay.
Abstract
We investigated the effect of MPTP‐induced lesion of the substantia nigra pars compacta (SNpc) dopaminergic neurons on GABAB receptors in the basal ganglia of mice and monkeys using receptor autoradiography and in situ hybridization. The extent of the lesion was measured with striatal catecholamine content, striatal binding of 125I‐RTI‐121 to dopamine transporter (DAT), and DAT expression in the SNpc. GABAB receptors in mice brain were evaluated using 3H‐CGP54626 and its expression was measured with oligonucleotides probes targeting the mRNAs of GABAB(1a+b), GABAB(1a), GABAB(1b), GABAB(2) subunits. In monkeys, 125I‐CGP64213 and selective probes for GABAB(1a+b) and GABAB(2) mRNAs were used. In mice, dopamine content, 125I‐RTI‐121 binding, and DAT expression were reduced by 44%, 40%, and 39% after a dose of 40 mg/kg of MPTP and 74%, 70%, and 34% after 120 mg/kg of MPTP, respectively. In monkeys, dopamine content and DAT expression were decreased by more than 90% and 80%, respectively. In the striatum and the subthalamic nucleus, GABAB receptors were unchanged following MPTP in both species. In the SNpc of mice, MPTP (120 mg/kg) induced a significant decrease of 3H‐CGP54626 binding (−10%) and of the expression of GABAB(1a+b) mRNA (−13%). The decrease of the expression of GABAB(1a+b) mRNA was correlated with dopamine content, 125I‐RTI‐121 binding and DAT expression. In MPTP‐treated monkeys, 125I‐CGP64213 binding (−40%), GABAB(1a+b) mRNA (−69%) and GABAB(2) mRNA (−66%) were also significantly decreased in the SNpc. Our results suggest that MPTP‐induced denervation is associated with a decrease of GABAB receptors restricted to the SNpc. These observations may be relevant to the pathophysiology of motor disorders involving dysfunction of the basal ganglia such as Parkinson disease. Synapse 40:225–234, 2001. © 2001 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/syn.1045
Affiliations:
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GABAB receptors: Correlation with dopamine concentrations and dopamine transporter</title><author><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), Québec, and Faculty of Pharmacy, Laval University, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Lavertu, Nadia" sort="Lavertu, Nadia" uniqKey="Lavertu N" first="Nadia" last="Lavertu">Nadia Lavertu</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), Québec, and Faculty of Pharmacy, Laval University, 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Blanchet</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Neuroscience Research Unit, Laval University Medical Center (CHUL), Québec, and Department of Medicine, Faculty of Medicine, Laval University, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bédard">Paul J. 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Qc</wicri:regionArea><wicri:noRegion>Qc</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="ISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2001-06-01">2001-06-01</date><biblScope unit="volume">40</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="225">225</biblScope><biblScope unit="page" to="234">234</biblScope></imprint><idno type="ISSN">0887-4476</idno></series><idno type="istex">8DD5BCF1B10708AE3857882704F6FE29F9090748</idno><idno type="DOI">10.1002/syn.1045</idno><idno type="ArticleID">SYN1045</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0887-4476</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Animals</term><term>Basal Ganglia (metabolism)</term><term>Basal Ganglia (physiopathology)</term><term>Benzoates (metabolism)</term><term>Cocaine (analogs & derivatives)</term><term>Cocaine (metabolism)</term><term>Corpus Striatum (metabolism)</term><term>Corpus Striatum (physiopathology)</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>GABA</term><term>Macaca fascicularis</term><term>Male</term><term>Membrane Glycoproteins (metabolism)</term><term>Membrane Transport Proteins (metabolism)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Nerve Tissue Proteins (metabolism)</term><term>Organophosphorus Compounds (metabolism)</term><term>Parkinson</term><term>Parkinsonian Disorders (chemically induced)</term><term>Parkinsonian Disorders (metabolism)</term><term>Parkinsonian Disorders (physiopathology)</term><term>Protein Subunits (genetics)</term><term>Protein Subunits (metabolism)</term><term>RNA, Messenger (metabolism)</term><term>Radioligand Assay</term><term>Receptors, GABA-B (genetics)</term><term>Receptors, GABA-B (metabolism)</term><term>Substantia Nigra (metabolism)</term><term>Substantia Nigra (physiopathology)</term><term>Subthalamic Nucleus (metabolism)</term><term>Subthalamic Nucleus (physiopathology)</term><term>autoradiography</term><term>dopamine</term><term>in situ hybridization</term><term>substantia nigra</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Cocaine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein Subunits</term><term>Receptors, GABA-B</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Benzoates</term><term>Cocaine</term><term>Dopamine</term><term>Membrane Glycoproteins</term><term>Membrane Transport Proteins</term><term>Nerve Tissue Proteins</term><term>Organophosphorus Compounds</term><term>Protein Subunits</term><term>RNA, Messenger</term><term>Receptors, GABA-B</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Dopamine Plasma Membrane Transport Proteins</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Basal Ganglia</term><term>Corpus Striatum</term><term>Parkinsonian Disorders</term><term>Substantia Nigra</term><term>Subthalamic Nucleus</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Basal Ganglia</term><term>Corpus Striatum</term><term>Parkinsonian Disorders</term><term>Substantia Nigra</term><term>Subthalamic Nucleus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>Macaca fascicularis</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Radioligand Assay</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We investigated the effect of MPTP‐induced lesion of the substantia nigra pars compacta (SNpc) dopaminergic neurons on GABAB receptors in the basal ganglia of mice and monkeys using receptor autoradiography and in situ hybridization. The extent of the lesion was measured with striatal catecholamine content, striatal binding of 125I‐RTI‐121 to dopamine transporter (DAT), and DAT expression in the SNpc. GABAB receptors in mice brain were evaluated using 3H‐CGP54626 and its expression was measured with oligonucleotides probes targeting the mRNAs of GABAB(1a+b), GABAB(1a), GABAB(1b), GABAB(2) subunits. In monkeys, 125I‐CGP64213 and selective probes for GABAB(1a+b) and GABAB(2) mRNAs were used. In mice, dopamine content, 125I‐RTI‐121 binding, and DAT expression were reduced by 44%, 40%, and 39% after a dose of 40 mg/kg of MPTP and 74%, 70%, and 34% after 120 mg/kg of MPTP, respectively. In monkeys, dopamine content and DAT expression were decreased by more than 90% and 80%, respectively. In the striatum and the subthalamic nucleus, GABAB receptors were unchanged following MPTP in both species. In the SNpc of mice, MPTP (120 mg/kg) induced a significant decrease of 3H‐CGP54626 binding (−10%) and of the expression of GABAB(1a+b) mRNA (−13%). The decrease of the expression of GABAB(1a+b) mRNA was correlated with dopamine content, 125I‐RTI‐121 binding and DAT expression. In MPTP‐treated monkeys, 125I‐CGP64213 binding (−40%), GABAB(1a+b) mRNA (−69%) and GABAB(2) mRNA (−66%) were also significantly decreased in the SNpc. Our results suggest that MPTP‐induced denervation is associated with a decrease of GABAB receptors restricted to the SNpc. These observations may be relevant to the pathophysiology of motor disorders involving dysfunction of the basal ganglia such as Parkinson disease. Synapse 40:225–234, 2001. © 2001 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name></noRegion><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bédard">Paul J. Bédard</name><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Goulet, Martin" sort="Goulet, Martin" uniqKey="Goulet M" first="Martin" last="Goulet">Martin Goulet</name><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><name sortKey="Lavertu, Nadia" sort="Lavertu, Nadia" uniqKey="Lavertu N" first="Nadia" last="Lavertu">Nadia Lavertu</name><name sortKey="Lemieux, Anne Arie" sort="Lemieux, Anne Arie" uniqKey="Lemieux A" first="Anne-Marie" last="Lemieux">Anne-Marie Lemieux</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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