Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson's disease?
Identifieur interne : 000F21 ( Main/Exploration ); précédent : 000F20; suivant : 000F22Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson's disease?
Auteurs : C. Laloux [France] ; F. Gouel [France] ; C. Lachaud [France] ; K. Timmerman [France] ; B. Do Van [France] ; A. Jonneaux [France] ; M. Petrault [France] ; G. Garcon [France] ; N. Rouaix [France] ; C. Moreau [France] ; R. Bordet [France] ; J A Duce [Australie] ; J C Devedjian [France] ; D. Devos [France]Source :
- Neurobiology of disease [ 1095-953X ] ; 2017.
Abstract
In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia.
DOI: 10.1016/j.nbd.2017.03.013
PubMed: 28363801
Affiliations:
- Australie, France
- Angleterre, Hauts-de-France, Nord-Pas-de-Calais, Yorkshire-et-Humber
- Leeds, Lille
- Université de Leeds
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Laloux</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><wicri:noRegion>59045 Lille cedex</wicri:noRegion><wicri:noRegion>59045 Lille cedex</wicri:noRegion></affiliation></author><author><name sortKey="Gouel, F" sort="Gouel, F" uniqKey="Gouel F" first="F" last="Gouel">F. 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Do Van</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><wicri:noRegion>59045 Lille cedex</wicri:noRegion><wicri:noRegion>59045 Lille cedex</wicri:noRegion></affiliation></author><author><name sortKey="Jonneaux, A" sort="Jonneaux, A" uniqKey="Jonneaux A" first="A" last="Jonneaux">A. Jonneaux</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><wicri:noRegion>59045 Lille cedex</wicri:noRegion><wicri:noRegion>59045 Lille cedex</wicri:noRegion></affiliation></author><author><name sortKey="Petrault, M" sort="Petrault, M" uniqKey="Petrault M" first="M" last="Petrault">M. Petrault</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><wicri:noRegion>59045 Lille cedex</wicri:noRegion><wicri:noRegion>59045 Lille cedex</wicri:noRegion></affiliation></author><author><name sortKey="Garcon, G" sort="Garcon, G" uniqKey="Garcon G" first="G" last="Garcon">G. Garcon</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur de Lille, EA4483-IMPECS, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur de Lille, EA4483-IMPECS, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Rouaix, N" sort="Rouaix, N" uniqKey="Rouaix N" first="N" last="Rouaix">N. Rouaix</name><affiliation wicri:level="1"><nlm:affiliation>Service de biochimie, dosage des catécholamines, et biologie moléculaire, CHRU de Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de biochimie, dosage des catécholamines, et biologie moléculaire, CHRU de Lille</wicri:regionArea><wicri:noRegion>CHRU de Lille</wicri:noRegion><wicri:noRegion>CHRU de Lille</wicri:noRegion></affiliation></author><author><name sortKey="Moreau, C" sort="Moreau, C" uniqKey="Moreau C" first="C" last="Moreau">C. Moreau</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille</wicri:regionArea><wicri:noRegion>Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille</wicri:noRegion><wicri:noRegion>Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille</wicri:noRegion></affiliation></author><author><name sortKey="Bordet, R" sort="Bordet, R" uniqKey="Bordet R" first="R" last="Bordet">R. Bordet</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><wicri:noRegion>59045 Lille cedex</wicri:noRegion><wicri:noRegion>59045 Lille cedex</wicri:noRegion></affiliation></author><author><name sortKey="Duce, J A" sort="Duce, J A" uniqKey="Duce J" first="J A" last="Duce">J A Duce</name><affiliation wicri:level="4"><nlm:affiliation>School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK; Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK; Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Devedjian, J C" sort="Devedjian, J C" uniqKey="Devedjian J" first="J C" last="Devedjian">J C Devedjian</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><wicri:noRegion>59045 Lille cedex</wicri:noRegion><wicri:noRegion>59045 Lille cedex</wicri:noRegion></affiliation></author><author><name sortKey="Devos, D" sort="Devos, D" uniqKey="Devos D" first="D" last="Devos">D. Devos</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille, France. Electronic address: david.devos@chru-lille.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille</wicri:regionArea><wicri:noRegion>Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille</wicri:noRegion><wicri:noRegion>Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28363801</idno><idno type="pmid">28363801</idno><idno type="doi">10.1016/j.nbd.2017.03.013</idno><idno type="wicri:Area/PubMed/Corpus">000918</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000918</idno><idno type="wicri:Area/PubMed/Curation">000915</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000915</idno><idno type="wicri:Area/PubMed/Checkpoint">000915</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000915</idno><idno type="wicri:Area/Ncbi/Merge">004552</idno><idno type="wicri:Area/Ncbi/Curation">004552</idno><idno type="wicri:Area/Ncbi/Checkpoint">004552</idno><idno type="wicri:Area/Main/Merge">000F16</idno><idno type="wicri:Area/Main/Curation">000F21</idno><idno type="wicri:Area/Main/Exploration">000F21</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson's disease?</title><author><name sortKey="Laloux, C" sort="Laloux, C" uniqKey="Laloux C" first="C" last="Laloux">C. Laloux</name><affiliation wicri:level="3"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><placeName><region type="region" nuts="2">Hauts-de-France</region><region type="old region" nuts="2">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Gouel, F" sort="Gouel, F" uniqKey="Gouel F" first="F" last="Gouel">F. Gouel</name><affiliation wicri:level="3"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><placeName><region type="region" nuts="2">Hauts-de-France</region><region type="old region" nuts="2">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Lachaud, C" sort="Lachaud, C" uniqKey="Lachaud C" first="C" last="Lachaud">C. Lachaud</name><affiliation wicri:level="3"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><placeName><region type="region" nuts="2">Hauts-de-France</region><region type="old region" nuts="2">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Timmerman, K" sort="Timmerman, K" uniqKey="Timmerman K" first="K" last="Timmerman">K. Timmerman</name><affiliation wicri:level="3"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><placeName><region type="region" nuts="2">Hauts-de-France</region><region type="old region" nuts="2">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Do Van, B" sort="Do Van, B" uniqKey="Do Van B" first="B" last="Do Van">B. Do Van</name><affiliation wicri:level="3"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><placeName><region type="region" nuts="2">Hauts-de-France</region><region type="old region" nuts="2">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Jonneaux, A" sort="Jonneaux, A" uniqKey="Jonneaux A" first="A" last="Jonneaux">A. Jonneaux</name><affiliation wicri:level="3"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><placeName><region type="region" nuts="2">Hauts-de-France</region><region type="old region" nuts="2">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Petrault, M" sort="Petrault, M" uniqKey="Petrault M" first="M" last="Petrault">M. Petrault</name><affiliation wicri:level="3"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><placeName><region type="region" nuts="2">Hauts-de-France</region><region type="old region" nuts="2">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Garcon, G" sort="Garcon, G" uniqKey="Garcon G" first="G" last="Garcon">G. Garcon</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur de Lille, EA4483-IMPECS, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur de Lille, EA4483-IMPECS, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Rouaix, N" sort="Rouaix, N" uniqKey="Rouaix N" first="N" last="Rouaix">N. Rouaix</name><affiliation wicri:level="1"><nlm:affiliation>Service de biochimie, dosage des catécholamines, et biologie moléculaire, CHRU de Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de biochimie, dosage des catécholamines, et biologie moléculaire, CHRU de Lille</wicri:regionArea><wicri:noRegion>CHRU de Lille</wicri:noRegion><wicri:noRegion>CHRU de Lille</wicri:noRegion></affiliation></author><author><name sortKey="Moreau, C" sort="Moreau, C" uniqKey="Moreau C" first="C" last="Moreau">C. Moreau</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille</wicri:regionArea><wicri:noRegion>Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille</wicri:noRegion><wicri:noRegion>Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille</wicri:noRegion></affiliation></author><author><name sortKey="Bordet, R" sort="Bordet, R" uniqKey="Bordet R" first="R" last="Bordet">R. Bordet</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><wicri:noRegion>59045 Lille cedex</wicri:noRegion><wicri:noRegion>59045 Lille cedex</wicri:noRegion></affiliation></author><author><name sortKey="Duce, J A" sort="Duce, J A" uniqKey="Duce J" first="J A" last="Duce">J A Duce</name><affiliation wicri:level="4"><nlm:affiliation>School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK; Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK; Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Devedjian, J C" sort="Devedjian, J C" uniqKey="Devedjian J" first="J C" last="Devedjian">J C Devedjian</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex</wicri:regionArea><wicri:noRegion>59045 Lille cedex</wicri:noRegion><wicri:noRegion>59045 Lille cedex</wicri:noRegion></affiliation></author><author><name sortKey="Devos, D" sort="Devos, D" uniqKey="Devos D" first="D" last="Devos">D. Devos</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille, France. Electronic address: david.devos@chru-lille.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille</wicri:regionArea><wicri:noRegion>Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille</wicri:noRegion><wicri:noRegion>Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille</wicri:noRegion></affiliation></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="eISSN">1095-953X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Angleterre</li><li>Hauts-de-France</li><li>Nord-Pas-de-Calais</li><li>Yorkshire-et-Humber</li></region><settlement><li>Leeds</li><li>Lille</li></settlement><orgName><li>Université de Leeds</li></orgName></list><tree><country name="France"><region name="Hauts-de-France"><name sortKey="Laloux, C" sort="Laloux, C" uniqKey="Laloux C" first="C" last="Laloux">C. Laloux</name></region><name sortKey="Bordet, R" sort="Bordet, R" uniqKey="Bordet R" first="R" last="Bordet">R. Bordet</name><name sortKey="Devedjian, J C" sort="Devedjian, J C" uniqKey="Devedjian J" first="J C" last="Devedjian">J C Devedjian</name><name sortKey="Devos, D" sort="Devos, D" uniqKey="Devos D" first="D" last="Devos">D. Devos</name><name sortKey="Do Van, B" sort="Do Van, B" uniqKey="Do Van B" first="B" last="Do Van">B. Do Van</name><name sortKey="Garcon, G" sort="Garcon, G" uniqKey="Garcon G" first="G" last="Garcon">G. Garcon</name><name sortKey="Gouel, F" sort="Gouel, F" uniqKey="Gouel F" first="F" last="Gouel">F. Gouel</name><name sortKey="Jonneaux, A" sort="Jonneaux, A" uniqKey="Jonneaux A" first="A" last="Jonneaux">A. Jonneaux</name><name sortKey="Lachaud, C" sort="Lachaud, C" uniqKey="Lachaud C" first="C" last="Lachaud">C. Lachaud</name><name sortKey="Moreau, C" sort="Moreau, C" uniqKey="Moreau C" first="C" last="Moreau">C. Moreau</name><name sortKey="Petrault, M" sort="Petrault, M" uniqKey="Petrault M" first="M" last="Petrault">M. Petrault</name><name sortKey="Rouaix, N" sort="Rouaix, N" uniqKey="Rouaix N" first="N" last="Rouaix">N. Rouaix</name><name sortKey="Timmerman, K" sort="Timmerman, K" uniqKey="Timmerman K" first="K" last="Timmerman">K. Timmerman</name></country><country name="Australie"><region name="Angleterre"><name sortKey="Duce, J A" sort="Duce, J A" uniqKey="Duce J" first="J A" last="Duce">J A Duce</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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