Neurochemical changes induced by high frequency stimulation of the subthalamic nucleus within neuronal metworks involved in motor circuits and their interactions with a L-Dopa treatment. A brain microdialysis study in intact and hemiparkinsonian rats.
Identifieur interne : 000781 ( Hal/Corpus ); précédent : 000780; suivant : 000782Neurochemical changes induced by high frequency stimulation of the subthalamic nucleus within neuronal metworks involved in motor circuits and their interactions with a L-Dopa treatment. A brain microdialysis study in intact and hemiparkinsonian rats.
Auteurs : Emilie LacombeSource :
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Abstract
High frequency stimulation (HFS) of the subthalamic nucleus (STN) counteracts the motor symptoms of Parkinson's disease (PD), but also diminishes dramatically the L-Dopa-induced dyskinesia (LID) following an important, or even total reduction of L-Dopa doses in stimulated patients. However, the precise mechanisms underlying the therapeutic effectiveness of deep brain stimulation are not elucidated yet. In particular, the possible interactions existing between the effects of both STN HFS and L-Dopa remain to be elucidated.
Our work was carried out in the anesthetized animal, intact or hemiparkinsonian, acutely or chronically treated with L-Dopa, and submitted or not to HFS depending on the experiments. In a first set of experiments, we analyzed in intact rats STN HFS-induced neurochemical modifications (variations of glutamate and GABA contents measured by brain microdialysis) occuring in structures away from STN but implicated in motor networks, such as Fr3 cortex, thalamic ventromedial nucleus and superior colliculus. In a second set of experiments, we tried to determine if STN HFS could modulate the response to a chronic or an acute L-Dopa treatment on the contents of dopamine or its metabolites (DOPAC and HVA), glutamate and GABA. The main results highlight a synergistic interaction between the effects of acute L-Dopa and those driven by HFS. Indeed, it appears that HFS stimulation stabilizes dopamine contents increased by acute L-Dopa, delaying its metabolism. These results could then bring interesting arguments concerning the beneficial effects of STN HFS observed in PD patients, in particular regarding the stabilization of motor fluctuations.
Altogether, these data give new arguments for a better understanding of STN HFS mechanisms, and bring new prospects justifying the importance of STN HFS as a powerful treatment of PD.
Our work was carried out in the anesthetized animal, intact or hemiparkinsonian, acutely or chronically treated with L-Dopa, and submitted or not to HFS depending on the experiments. In a first set of experiments, we analyzed in intact rats STN HFS-induced neurochemical modifications (variations of glutamate and GABA contents measured by brain microdialysis) occuring in structures away from STN but implicated in motor networks, such as Fr3 cortex, thalamic ventromedial nucleus and superior colliculus. In a second set of experiments, we tried to determine if STN HFS could modulate the response to a chronic or an acute L-Dopa treatment on the contents of dopamine or its metabolites (DOPAC and HVA), glutamate and GABA. The main results highlight a synergistic interaction between the effects of acute L-Dopa and those driven by HFS. Indeed, it appears that HFS stimulation stabilizes dopamine contents increased by acute L-Dopa, delaying its metabolism. These results could then bring interesting arguments concerning the beneficial effects of STN HFS observed in PD patients, in particular regarding the stabilization of motor fluctuations.
Altogether, these data give new arguments for a better understanding of STN HFS mechanisms, and bring new prospects justifying the importance of STN HFS as a powerful treatment of PD.
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Etude par microdialyse intracérébrale chez le rat sain et hémiparkinsonien.</title><author><name sortKey="Lacombe, Emilie" sort="Lacombe, Emilie" uniqKey="Lacombe E" first="Emilie" last="Lacombe">Emilie Lacombe</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-3062" status="OLD"><orgName>Dynamique des Reseaux Neuronaux</orgName><desc><address><addrLine>Universite Joseph Fourier 2280, Rue de La Piscine 38400 ST MARTIN D HERES</addrLine><country key="FR"></country></address></desc><listRelation><relation active="#struct-51016" type="direct"></relation><relation name="U704" active="#struct-303623" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-51016" type="direct"><org type="institution" xml:id="struct-51016" status="OLD"> <idno type="IdRef">026404796</idno> <orgName>Université Joseph Fourier - Grenoble 1</orgName> <orgName type="acronym">UJF</orgName> <date type="end">2015-12-31</date> <desc> <address> <addrLine>BP 53 - 38041 Grenoble Cedex 9</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ujf-grenoble.fr/</ref> </desc></org></tutelle><tutelle name="U704" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:tel-00152498</idno><idno type="halId">tel-00152498</idno><idno type="halUri">https://tel.archives-ouvertes.fr/tel-00152498</idno><idno type="url">https://tel.archives-ouvertes.fr/tel-00152498</idno><date when="2007-04-27">2007-04-27</date><idno type="wicri:Area/Hal/Corpus">000781</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Neurochemical changes induced by high frequency stimulation of the subthalamic nucleus within neuronal metworks involved in motor circuits and their interactions with a L-Dopa treatment. A brain microdialysis study in intact and hemiparkinsonian rats.</title><title xml:lang="fr">MODIFICATIONS NEUROCHIMIQUES INDUITES PAR LA STIMULATION HAUTE FREQUENCE DU NOYAU SOUS-THALAMIQUE AU SEIN DES RESEAUX NEURONAUX IMPLIQUES DANS LES CIRCUITS MOTEURS ET LEURS INTERACTIONS AVEC UN TRAITEMENT A LA L-DOPA
Etude par microdialyse intracérébrale chez le rat sain et hémiparkinsonien.</title><author><name sortKey="Lacombe, Emilie" sort="Lacombe, Emilie" uniqKey="Lacombe E" first="Emilie" last="Lacombe">Emilie Lacombe</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-3062" status="OLD"><orgName>Dynamique des Reseaux Neuronaux</orgName><desc><address><addrLine>Universite Joseph Fourier 2280, Rue de La Piscine 38400 ST MARTIN D HERES</addrLine><country key="FR"></country></address></desc><listRelation><relation active="#struct-51016" type="direct"></relation><relation name="U704" active="#struct-303623" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-51016" type="direct"><org type="institution" xml:id="struct-51016" status="OLD"> <idno type="IdRef">026404796</idno> <orgName>Université Joseph Fourier - Grenoble 1</orgName> <orgName type="acronym">UJF</orgName> <date type="end">2015-12-31</date> <desc> <address> <addrLine>BP 53 - 38041 Grenoble Cedex 9</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ujf-grenoble.fr/</ref> </desc></org></tutelle><tutelle name="U704" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author></analytic></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>6-OHDA rat</term><term>Fr3 cortex</term><term>L-Dopa treatment</term><term>Parkinson's disease</term><term>brain microdialysis</term><term>subthalamic nucleus high frequency stimulation</term><term>superior colliculus</term><term>thalamic ventromedial nucleus</term></keywords><keywords scheme="mix" xml:lang="fr"><term>GABA</term><term>GABA.</term><term>Maladie de Parkinson</term><term>colliculus supérieur</term><term>cortex Fr3</term><term>dopamine</term><term>glutamate</term><term>microdialyse intracérébrale</term><term>noyau ventromédian du thalamus</term><term>rat 6-OHDA</term><term>stimulation haute fréquence du noyau sous-thalamique</term><term>striatum</term><term>traitement L-Dopa</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">High frequency stimulation (HFS) of the subthalamic nucleus (STN) counteracts the motor symptoms of Parkinson's disease (PD), but also diminishes dramatically the L-Dopa-induced dyskinesia (LID) following an important, or even total reduction of L-Dopa doses in stimulated patients. However, the precise mechanisms underlying the therapeutic effectiveness of deep brain stimulation are not elucidated yet. In particular, the possible interactions existing between the effects of both STN HFS and L-Dopa remain to be elucidated.
Our work was carried out in the anesthetized animal, intact or hemiparkinsonian, acutely or chronically treated with L-Dopa, and submitted or not to HFS depending on the experiments. In a first set of experiments, we analyzed in intact rats STN HFS-induced neurochemical modifications (variations of glutamate and GABA contents measured by brain microdialysis) occuring in structures away from STN but implicated in motor networks, such as Fr3 cortex, thalamic ventromedial nucleus and superior colliculus. In a second set of experiments, we tried to determine if STN HFS could modulate the response to a chronic or an acute L-Dopa treatment on the contents of dopamine or its metabolites (DOPAC and HVA), glutamate and GABA. The main results highlight a synergistic interaction between the effects of acute L-Dopa and those driven by HFS. Indeed, it appears that HFS stimulation stabilizes dopamine contents increased by acute L-Dopa, delaying its metabolism. These results could then bring interesting arguments concerning the beneficial effects of STN HFS observed in PD patients, in particular regarding the stabilization of motor fluctuations.
Altogether, these data give new arguments for a better understanding of STN HFS mechanisms, and bring new prospects justifying the importance of STN HFS as a powerful treatment of PD.</div></front></TEI><hal api="V3"><titleStmt><title xml:lang="en">Neurochemical changes induced by high frequency stimulation of the subthalamic nucleus within neuronal metworks involved in motor circuits and their interactions with a L-Dopa treatment. A brain microdialysis study in intact and hemiparkinsonian rats.</title><title xml:lang="fr">MODIFICATIONS NEUROCHIMIQUES INDUITES PAR LA STIMULATION HAUTE FREQUENCE DU NOYAU SOUS-THALAMIQUE AU SEIN DES RESEAUX NEURONAUX IMPLIQUES DANS LES CIRCUITS MOTEURS ET LEURS INTERACTIONS AVEC UN TRAITEMENT A LA L-DOPA
Etude par microdialyse intracérébrale chez le rat sain et hémiparkinsonien.</title><author role="aut"><persName><forename type="first">Emilie</forename><surname>Lacombe</surname></persName><email type="md5">f382a589a6baf1abe06768196c4b0ad4</email><email type="domain">ibdml.univ-mrs.fr</email><idno type="halauthorid">185828</idno><affiliation ref="#struct-3062"></affiliation></author><editor role="depositor"><persName><forename>Emilie</forename><surname>Lacombe</surname></persName><email type="md5">f382a589a6baf1abe06768196c4b0ad4</email><email type="domain">ibdml.univ-mrs.fr</email></editor></titleStmt><editionStmt><edition n="v1" type="current"><date type="whenSubmitted">2007-06-07 09:11:35</date><date type="whenModified">2007-06-07 12:45:13</date><date type="whenReleased">2007-06-07 12:45:13</date><date type="whenProduced">2007-04-27</date><date type="whenEndEmbargoed">2007-06-07</date><ref type="file" target="https://tel.archives-ouvertes.fr/tel-00152498/document"><date notBefore="2007-06-07"></date></ref><ref type="file" n="1" target="https://tel.archives-ouvertes.fr/tel-00152498/file/THESE_fichier_TEL.pdf"><date notBefore="2007-06-07"></date></ref></edition><respStmt><resp>contributor</resp><name key="118587"><persName><forename>Emilie</forename><surname>Lacombe</surname></persName><email type="md5">f382a589a6baf1abe06768196c4b0ad4</email><email type="domain">ibdml.univ-mrs.fr</email></name></respStmt></editionStmt><publicationStmt><distributor>CCSD</distributor><idno type="halId">tel-00152498</idno><idno type="halUri">https://tel.archives-ouvertes.fr/tel-00152498</idno><idno type="halBibtex">lacombe:tel-00152498</idno><idno type="halRefHtml">Neurosciences [q-bio.NC]. Université Joseph-Fourier - Grenoble I, 2007. Français</idno><idno type="halRef">Neurosciences [q-bio.NC]. Université Joseph-Fourier - Grenoble I, 2007. Français</idno></publicationStmt><seriesStmt><idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno><idno type="stamp" n="UJF">Thèses de l'Université Joseph Fourier</idno><idno type="stamp" n="UNIV-GRENOBLE1" p="UGA">Université Joseph Fourier - Grenoble I</idno><idno type="stamp" n="UGA">HAL Grenoble Alpes</idno></seriesStmt><notesStmt></notesStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Neurochemical changes induced by high frequency stimulation of the subthalamic nucleus within neuronal metworks involved in motor circuits and their interactions with a L-Dopa treatment. A brain microdialysis study in intact and hemiparkinsonian rats.</title><title xml:lang="fr">MODIFICATIONS NEUROCHIMIQUES INDUITES PAR LA STIMULATION HAUTE FREQUENCE DU NOYAU SOUS-THALAMIQUE AU SEIN DES RESEAUX NEURONAUX IMPLIQUES DANS LES CIRCUITS MOTEURS ET LEURS INTERACTIONS AVEC UN TRAITEMENT A LA L-DOPA
Etude par microdialyse intracérébrale chez le rat sain et hémiparkinsonien.</title><author role="aut"><persName><forename type="first">Emilie</forename><surname>Lacombe</surname></persName><email type="md5">f382a589a6baf1abe06768196c4b0ad4</email><email type="domain">ibdml.univ-mrs.fr</email><idno type="halauthorid">185828</idno><affiliation ref="#struct-3062"></affiliation></author></analytic><monogr><imprint><date type="dateDefended">2007-04-27</date></imprint><authority type="institution">Université Joseph-Fourier - Grenoble I</authority><authority type="school">Chimie et Sciences du Vivant</authority><authority type="supervisor">Marc Savasta(marc.savasta@ujf-grenoble.fr)</authority><authority type="jury">Pr Claude FEUERSTEIN (Président de jury)</authority><authority type="jury">Dr Abdelhamid BENAZZOUZ (Rapporteur)</authority><authority type="jury">Dr Pascal SALIN (Rapporteur)</authority><authority type="jury">Dr Marie-Louise KEMEL (Examinatrice)</authority><authority type="jury">Pr Emmanuel BROUSSOLLE (Examinateur)</authority><authority type="jury">Dr Marc SAVASTA (Directeur de thèse)</authority></monogr></biblStruct></sourceDesc><profileDesc><langUsage><language ident="fr">French</language></langUsage><textClass><keywords scheme="author"><term xml:lang="en">Parkinson's disease</term><term xml:lang="en">subthalamic nucleus high frequency stimulation</term><term xml:lang="en">brain microdialysis</term><term xml:lang="en">L-Dopa treatment</term><term xml:lang="en">Fr3 cortex</term><term xml:lang="en">thalamic ventromedial nucleus</term><term xml:lang="en">superior colliculus</term><term xml:lang="en">6-OHDA rat</term><term xml:lang="fr">GABA</term><term xml:lang="fr">Maladie de Parkinson</term><term xml:lang="fr">stimulation haute fréquence du noyau sous-thalamique</term><term xml:lang="fr">microdialyse intracérébrale</term><term xml:lang="fr">traitement L-Dopa</term><term xml:lang="fr">striatum</term><term xml:lang="fr">cortex Fr3</term><term xml:lang="fr">noyau ventromédian du thalamus</term><term xml:lang="fr">colliculus supérieur</term><term xml:lang="fr">rat 6-OHDA</term><term xml:lang="fr">dopamine</term><term xml:lang="fr">glutamate</term><term xml:lang="fr">GABA.</term></keywords><classCode scheme="halDomain" n="sdv.neu">Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]</classCode><classCode scheme="halTypology" n="THESE">Theses</classCode></textClass><abstract xml:lang="en">High frequency stimulation (HFS) of the subthalamic nucleus (STN) counteracts the motor symptoms of Parkinson's disease (PD), but also diminishes dramatically the L-Dopa-induced dyskinesia (LID) following an important, or even total reduction of L-Dopa doses in stimulated patients. However, the precise mechanisms underlying the therapeutic effectiveness of deep brain stimulation are not elucidated yet. In particular, the possible interactions existing between the effects of both STN HFS and L-Dopa remain to be elucidated.
Our work was carried out in the anesthetized animal, intact or hemiparkinsonian, acutely or chronically treated with L-Dopa, and submitted or not to HFS depending on the experiments. In a first set of experiments, we analyzed in intact rats STN HFS-induced neurochemical modifications (variations of glutamate and GABA contents measured by brain microdialysis) occuring in structures away from STN but implicated in motor networks, such as Fr3 cortex, thalamic ventromedial nucleus and superior colliculus. In a second set of experiments, we tried to determine if STN HFS could modulate the response to a chronic or an acute L-Dopa treatment on the contents of dopamine or its metabolites (DOPAC and HVA), glutamate and GABA. The main results highlight a synergistic interaction between the effects of acute L-Dopa and those driven by HFS. Indeed, it appears that HFS stimulation stabilizes dopamine contents increased by acute L-Dopa, delaying its metabolism. These results could then bring interesting arguments concerning the beneficial effects of STN HFS observed in PD patients, in particular regarding the stabilization of motor fluctuations.
Altogether, these data give new arguments for a better understanding of STN HFS mechanisms, and bring new prospects justifying the importance of STN HFS as a powerful treatment of PD.</abstract><abstract xml:lang="fr">La stimulation à haute fréquence (SHF) du noyau sous-thalamique (NST) permet de traiter l'ensemble des symptômes moteurs de la maladie de Parkinson (MP), mais aussi d'atténuer l'apparition les dyskinésies L-Dopa induites, grâce notamment à une réduction massive, voire complète, des prises de L-Dopa chez les patients stimulés. Toutefois, les mécanismes in fine qui sous-tendent l'efficacité thérapeutique de la SHF du NST chez l'homme ne sont pas encore élucidés, tout comme les possibles interactions pouvant exister entre les effets induits par la SHF du NST et ceux (synergiques ou non) d'un traitement à la L-DOPA.
Notre travail a porté principalement sur l'animal anesthésié, sain ou hémiparkinsonien, traité de manière chronique ou aiguë à la L-Dopa, et soumis ou non à la SHF du NST. Dans une première partie expérimentale, nous avons analysé chez le rat sain les modifications neurochimiques (variations des contenus en glutamate et en GABA mesurées par microdialyse intracérébrale) induites par la SHF du NST sur des structures situées à distance du NST mais impliquées directement ou indirectement dans les circuits moteurs, comme la region Fr3 du cortex moteur, le colliculus supérieur et le noyau ventro-médian du thalamus.Dans une deuxième partie, nous avons essayé de déterminer si la SHF du NST pouvait modifier la réponse à la L-Dopa (suite à un traitement chronique ou aigu) sur les contenus en dopamine (et ses métabolites DOPAC et HVA), en glutamate et en GABA. Les principaux résultats obtenus mettent en exergue une interaction synergique entre les effets d'une injection unique de L-Dopa et ceux induits par la SHF du NST. En effet, il apparaît que cette stimulation stabilise les taux élevés de dopamine suite au traitement L-Dopa, retardant ainsi son métabolisme. Ces résultats pourraient donc apporter de arguments intéressants concernant les effets bénéfiques de la SHF du NST observés chez les malades parkinsoniens, notamment dans la stabilisation des fluctuations motrices.
Les données obtenues au cours de ce travail doctoral apportent de nouveaux arguments pour la compréhension des mécanismes de la SHF du NST, et amènent de nouvelles perspectives justifiant l'intérêt thérapeutique de la SHF dans la maladie de Parkinson.</abstract></profileDesc></hal></record>Pour manipuler ce document sous Unix (Dilib)
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