High-frequency stimulation of the subthalamic nucleus modifies the expression of vesicular glutamate transporters in basal ganglia in a rat model of Parkinson’s disease
Identifieur interne : 000095 ( France/Analysis ); précédent : 000094; suivant : 000096High-frequency stimulation of the subthalamic nucleus modifies the expression of vesicular glutamate transporters in basal ganglia in a rat model of Parkinson’s disease
Auteurs : Mathieu Favier [France] ; Carole Carcenac [France] ; Guillaume Drui [France] ; Sabrina Boulet [France] ; Salah El Mestikawy [France, Canada] ; Marc Savasta [France]Source :
- BMC Neuroscience [ 1471-2202 ] ; 2013.
Abstract
It has been suggested that glutamatergic system hyperactivity may be related to the pathogenesis of Parkinson’s disease (PD). Vesicular glutamate transporters (VGLUT1-3) import glutamate into synaptic vesicles and are key anatomical and functional markers of glutamatergic excitatory transmission. Both VGLUT1 and VGLUT2 have been identified as definitive markers of glutamatergic neurons, but VGLUT 3 is also expressed by non glutamatergic neurons. VGLUT1 and VGLUT2 are thought to be expressed in a complementary manner in the cortex and the thalamus (VL/VM), in glutamatergic neurons involved in different physiological functions. Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced PD. STN-HFS is highly effective, but its mechanisms of action remain unclear. This study examines the effect of STN-HFS on VGLUT1-3 expression in different brain nuclei involved in motor circuits, namely the basal ganglia (BG) network, in normal and 6-hydroxydopamine (6-OHDA) lesioned rats.
Here we report that: 1) Dopamine(DA)-depletion did not affect VGLUT1 and VGLUT3 expression but significantly decreased that of VGLUT2 in almost all BG structures studied; 2) STN-HFS did not change VGLUT1-3 expression in the different brain areas of normal rats while, on the contrary, it systematically induced a significant increase of their expression in DA-depleted rats and 3) STN-HFS reversed the decrease in VGLUT2 expression induced by the DA-depletion.
These results show for the first time a comparative analysis of changes of expression for the three VGLUTs induced by STN-HFS in the BG network of normal and hemiparkinsonian rats. They provide evidence for the involvement of VGLUT2 in the modulation of BG cicuits and in particular that of thalamostriatal and thalamocortical pathways suggesting their key role in its therapeutic effects for alleviating PD motor symptoms.
Url:
DOI: 10.1186/1471-2202-14-152
PubMed: 24308494
PubMed Central: 4234365
Affiliations:
- Canada, France
- Auvergne-Rhône-Alpes, Québec, Rhône-Alpes, Île-de-France
- Cedex 9, Grenoble, Montréal, Paris
- Université McGill, Université Pierre-et-Marie-Curie
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PMC:4234365Le document en format XML
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9</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Cedex 9</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I2">Université de Grenoble, Grenoble F- 38042, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Grenoble, Grenoble F- 38042</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Carcenac, Carole" sort="Carcenac, Carole" uniqKey="Carcenac C" first="Carole" last="Carcenac">Carole Carcenac</name><affiliation wicri:level="3"><nlm:aff id="I1">Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Cedex 9</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I2">Université de Grenoble, Grenoble F- 38042, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Grenoble, Grenoble F- 38042</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Drui, Guillaume" sort="Drui, Guillaume" uniqKey="Drui G" first="Guillaume" last="Drui">Guillaume Drui</name><affiliation wicri:level="3"><nlm:aff id="I1">Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Cedex 9</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I2">Université de Grenoble, Grenoble F- 38042, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Grenoble, Grenoble F- 38042</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Boulet, Sabrina" sort="Boulet, Sabrina" uniqKey="Boulet S" first="Sabrina" last="Boulet">Sabrina Boulet</name><affiliation wicri:level="3"><nlm:aff id="I1">Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Cedex 9</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I2">Université de Grenoble, Grenoble F- 38042, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Grenoble, Grenoble F- 38042</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="El Mestikawy, Salah" sort="El Mestikawy, Salah" uniqKey="El Mestikawy S" first="Salah" last="El Mestikawy">Salah El Mestikawy</name><affiliation wicri:level="4"><nlm:aff id="I4">Institut National de la Santé et de la Recherche Médicale (INSERM), U952, Université Pierre et Marie Curie, Paris F-75005, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale (INSERM), U952, Université Pierre et Marie Curie, Paris F-75005</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="I5">Centre National de la Recherche Scientifique (CNRS) UMR 7224, Paris F-75005, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de la Recherche Scientifique (CNRS) UMR 7224, Paris F-75005</wicri:regionArea><wicri:noRegion>75005</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="I6">Université Pierre et Marie Curie (UPMC) Paris 06, Pathophysiology of Central Nervous System Disorders, Paris F-75005, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Pierre et Marie Curie (UPMC) Paris 06, Pathophysiology of Central Nervous System Disorders, Paris F-75005</wicri:regionArea><wicri:noRegion>75005</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="I7">Department of Psychiatry, Douglas Hospital Research Center, McGill University, 6875, boulevard Lasalle, Verdun, QC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry, Douglas Hospital Research Center, McGill University, 6875, boulevard Lasalle, Verdun, QC</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name><affiliation wicri:level="1"><nlm:aff id="I1">Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9</wicri:regionArea><wicri:noRegion>38043, Cedex 9</wicri:noRegion><wicri:noRegion>38043, Cedex 9</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Université de Grenoble, Grenoble F- 38042, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Grenoble, Grenoble F- 38042</wicri:regionArea><wicri:noRegion>38042</wicri:noRegion><wicri:noRegion>38042</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I3">Centre Hospitalier Universitaire de Grenoble, BP217, Grenoble F-38043, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Universitaire de Grenoble, BP217, Grenoble F-38043</wicri:regionArea><wicri:noRegion>38043</wicri:noRegion><placeName><settlement type="city">Grenoble</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author></analytic><series><title level="j">BMC Neuroscience</title><idno type="eISSN">1471-2202</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>It has been suggested that glutamatergic system hyperactivity may be related to the pathogenesis of Parkinson’s disease (PD). Vesicular glutamate transporters (VGLUT1-3) import glutamate into synaptic vesicles and are key anatomical and functional markers of glutamatergic excitatory transmission. Both VGLUT1 and VGLUT2 have been identified as definitive markers of glutamatergic neurons, but VGLUT 3 is also expressed by non glutamatergic neurons. VGLUT1 and VGLUT2 are thought to be expressed in a complementary manner in the cortex and the thalamus (VL/VM), in glutamatergic neurons involved in different physiological functions. Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced PD. STN-HFS is highly effective, but its mechanisms of action remain unclear. This study examines the effect of STN-HFS on VGLUT1-3 expression in different brain nuclei involved in motor circuits, namely the basal ganglia (BG) network, in normal and 6-hydroxydopamine (6-OHDA) lesioned rats.</p></sec><sec><title>Results</title><p>Here we report that: 1) Dopamine(DA)-depletion did not affect VGLUT1 and VGLUT3 expression but significantly decreased that of VGLUT2 in almost all BG structures studied; 2) STN-HFS did not change VGLUT1-3 expression in the different brain areas of normal rats while, on the contrary, it systematically induced a significant increase of their expression in DA-depleted rats and 3) STN-HFS reversed the decrease in VGLUT2 expression induced by the DA-depletion.</p></sec><sec><title>Conclusions</title><p>These results show for the first time a comparative analysis of changes of expression for the three VGLUTs induced by STN-HFS in the BG network of normal and hemiparkinsonian rats. 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Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Navailles, S" uniqKey="Navailles S">S Navailles</name></author><author><name sortKey="Benazzouz, A" uniqKey="Benazzouz A">A Benazzouz</name></author><author><name sortKey="Bioulac, B" uniqKey="Bioulac B">B Bioulac</name></author><author><name sortKey="Gross, C" uniqKey="Gross C">C Gross</name></author><author><name sortKey="De Deurwaerdere, P" uniqKey="De Deurwaerdere P">P De Deurwaerdère</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Temel, Y" uniqKey="Temel Y">Y Temel</name></author><author><name sortKey="Boothman, Lj" uniqKey="Boothman L">LJ Boothman</name></author><author><name sortKey="Blokland, A" uniqKey="Blokland A">A Blokland</name></author><author><name sortKey="Magill, Pj" uniqKey="Magill P">PJ Magill</name></author><author><name sortKey="Steinbusch, Hw" uniqKey="Steinbusch H">HW Steinbusch</name></author><author><name sortKey="Visser Vandewalle, V" uniqKey="Visser Vandewalle V">V Visser-Vandewalle</name></author><author><name sortKey="Sharp, T" uniqKey="Sharp T">T Sharp</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Québec</li><li>Rhône-Alpes</li><li>Île-de-France</li></region><settlement><li>Cedex 9</li><li>Grenoble</li><li>Montréal</li><li>Paris</li></settlement><orgName><li>Université McGill</li><li>Université Pierre-et-Marie-Curie</li></orgName></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Favier, Mathieu" sort="Favier, Mathieu" uniqKey="Favier M" first="Mathieu" last="Favier">Mathieu Favier</name></region><name sortKey="Boulet, Sabrina" sort="Boulet, Sabrina" uniqKey="Boulet S" first="Sabrina" last="Boulet">Sabrina Boulet</name><name sortKey="Boulet, Sabrina" sort="Boulet, Sabrina" uniqKey="Boulet S" first="Sabrina" last="Boulet">Sabrina Boulet</name><name sortKey="Carcenac, Carole" sort="Carcenac, Carole" uniqKey="Carcenac C" first="Carole" last="Carcenac">Carole Carcenac</name><name sortKey="Carcenac, Carole" sort="Carcenac, Carole" uniqKey="Carcenac C" first="Carole" last="Carcenac">Carole Carcenac</name><name sortKey="Drui, Guillaume" sort="Drui, Guillaume" uniqKey="Drui G" first="Guillaume" last="Drui">Guillaume Drui</name><name sortKey="Drui, Guillaume" sort="Drui, Guillaume" uniqKey="Drui G" first="Guillaume" last="Drui">Guillaume Drui</name><name sortKey="El Mestikawy, Salah" sort="El Mestikawy, Salah" uniqKey="El Mestikawy S" first="Salah" last="El Mestikawy">Salah El Mestikawy</name><name sortKey="El Mestikawy, Salah" sort="El Mestikawy, Salah" uniqKey="El Mestikawy S" first="Salah" last="El Mestikawy">Salah El Mestikawy</name><name sortKey="El Mestikawy, Salah" sort="El Mestikawy, Salah" uniqKey="El Mestikawy S" first="Salah" last="El Mestikawy">Salah El Mestikawy</name><name sortKey="Favier, Mathieu" sort="Favier, Mathieu" uniqKey="Favier M" first="Mathieu" last="Favier">Mathieu Favier</name><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name></country><country name="Canada"><region name="Québec"><name sortKey="El Mestikawy, Salah" sort="El Mestikawy, Salah" uniqKey="El Mestikawy S" first="Salah" last="El Mestikawy">Salah El Mestikawy</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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