Intrastriatal grafts of embryonic mesencephalic rat neurons genetically modified using an adenovirus encoding human Cu/Zn superoxide dismutase
Identifieur interne : 004432 ( Main/Exploration ); précédent : 004431; suivant : 004433Intrastriatal grafts of embryonic mesencephalic rat neurons genetically modified using an adenovirus encoding human Cu/Zn superoxide dismutase
Auteurs : M. Barkats [France] ; N. Nakao [Suède] ; E. M. Grasbon-Frodl [Suède] ; A. Bilang-Bleuel [France] ; F. Revah [France] ; J. Mallet [France] ; P. Brundin [Suède]Source :
- Neuroscience [ 0306-4522 ] ; 1997.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
Intrastriatal grafting of embryonic dopamine-containing neurons is a promising approach for treating clinical and experimental Parkinson's disease. However, neuropathological analyses of grafted patients and transplanted rats have demonstrated that the survival of grafted dopamine neurons is relatively poor. In the present study, we pursued a strategy of transferring a potentially neuroprotective gene into rat embryonic mesencephalic rat cells in vitro, before grafting them into the denervated striatum of 6-hydroxydopamine-lesioned rats. We performed intrastriatal grafts of embryonic day 14 mesencephalic cells infected with replication-defective adenoviruses bearing either the human copper-zinc superoxide dismutase gene or, as a control, the E. coli lac Z marker gene. The transgenes were expressed in the grafts four days after transplantation and the expression persisted for at least five weeks thereafter. After five weeks postgrafting, there was more extensive functional recovery in the superoxide dismutase group as compared to the control (uninfected cells) and β-galactosidase groups. The functional recovery was significantly correlated with the number of tyrosine hydroxylase-positive cells in the grafts, although the clear trend to increased survival of the dopamine neurons in the superoxide dismutase grafts did not reach statistical significance. Only a moderate inflammatory reaction was revealed by OX-42 immunostaining in all groups. suggesting that ex vivo gene transfer using adenoviral vectors is a promising method for delivering functional proteins into brain grafts.
Affiliations:
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Barkats</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, UMR CNRS C9923, Hôpital de la Pitié Salpêtrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Nakao, N" sort="Nakao, N" uniqKey="Nakao N" first="N." last="Nakao">N. Nakao</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Section for Neuronal Survival, Department of Physiology and Neuroscience, University of Lund</s1><s2>Lund</s2><s3>SWE</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Suède</country><wicri:noRegion>Lund</wicri:noRegion></affiliation></author><author><name sortKey="Grasbon Frodl, E M" sort="Grasbon Frodl, E M" uniqKey="Grasbon Frodl E" first="E. M." last="Grasbon-Frodl">E. M. Grasbon-Frodl</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Section for Neuronal Survival, Department of Physiology and Neuroscience, University of Lund</s1><s2>Lund</s2><s3>SWE</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Suède</country><wicri:noRegion>Lund</wicri:noRegion></affiliation></author><author><name sortKey="Bilang Bleuel, A" sort="Bilang Bleuel, A" uniqKey="Bilang Bleuel A" first="A." last="Bilang-Bleuel">A. Bilang-Bleuel</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, UMR CNRS C9923, Hôpital de la Pitié Salpêtrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Revah, F" sort="Revah, F" uniqKey="Revah F" first="F." last="Revah">F. Revah</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Gencell Rhône-Poulenc-Rorer</s1><s2>Vitry sur Seine</s2><s3>FRA</s3><sZ>5 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Vitry sur Seine</wicri:noRegion><wicri:noRegion>Gencell Rhône-Poulenc-Rorer</wicri:noRegion><wicri:noRegion>Gencell Rhône-Poulenc-Rorer</wicri:noRegion></affiliation></author><author><name sortKey="Mallet, J" sort="Mallet, J" uniqKey="Mallet J" first="J." last="Mallet">J. Mallet</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, UMR CNRS C9923, Hôpital de la Pitié Salpêtrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Brundin, P" sort="Brundin, P" uniqKey="Brundin P" first="P." last="Brundin">P. Brundin</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Section for Neuronal Survival, Department of Physiology and Neuroscience, University of Lund</s1><s2>Lund</s2><s3>SWE</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Suède</country><wicri:noRegion>Lund</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Neuroscience</title><title level="j" type="abbreviated">Neuroscience</title><idno type="ISSN">0306-4522</idno><imprint><date when="1997">1997</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neuroscience</title><title level="j" type="abbreviated">Neuroscience</title><idno type="ISSN">0306-4522</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Corpus striatum</term><term>Graft</term><term>Human</term><term>Midbrain</term><term>Parkinson disease</term><term>Rat</term><term>Superoxide dismutase</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Greffe</term><term>Corps strié</term><term>Mésencéphale</term><term>Homme</term><term>Superoxide dismutase</term><term>Parkinson maladie</term><term>Rat</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Intrastriatal grafting of embryonic dopamine-containing neurons is a promising approach for treating clinical and experimental Parkinson's disease. However, neuropathological analyses of grafted patients and transplanted rats have demonstrated that the survival of grafted dopamine neurons is relatively poor. In the present study, we pursued a strategy of transferring a potentially neuroprotective gene into rat embryonic mesencephalic rat cells in vitro, before grafting them into the denervated striatum of 6-hydroxydopamine-lesioned rats. We performed intrastriatal grafts of embryonic day 14 mesencephalic cells infected with replication-defective adenoviruses bearing either the human copper-zinc superoxide dismutase gene or, as a control, the E. coli lac Z marker gene. The transgenes were expressed in the grafts four days after transplantation and the expression persisted for at least five weeks thereafter. After five weeks postgrafting, there was more extensive functional recovery in the superoxide dismutase group as compared to the control (uninfected cells) and β-galactosidase groups. The functional recovery was significantly correlated with the number of tyrosine hydroxylase-positive cells in the grafts, although the clear trend to increased survival of the dopamine neurons in the superoxide dismutase grafts did not reach statistical significance. Only a moderate inflammatory reaction was revealed by OX-42 immunostaining in all groups. suggesting that ex vivo gene transfer using adenoviral vectors is a promising method for delivering functional proteins into brain grafts.</div></front></TEI><affiliations><list><country><li>France</li><li>Suède</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Barkats, M" sort="Barkats, M" uniqKey="Barkats M" first="M." last="Barkats">M. Barkats</name></region><name sortKey="Bilang Bleuel, A" sort="Bilang Bleuel, A" uniqKey="Bilang Bleuel A" first="A." last="Bilang-Bleuel">A. Bilang-Bleuel</name><name sortKey="Mallet, J" sort="Mallet, J" uniqKey="Mallet J" first="J." last="Mallet">J. Mallet</name><name sortKey="Revah, F" sort="Revah, F" uniqKey="Revah F" first="F." last="Revah">F. Revah</name></country><country name="Suède"><noRegion><name sortKey="Nakao, N" sort="Nakao, N" uniqKey="Nakao N" first="N." last="Nakao">N. Nakao</name></noRegion><name sortKey="Brundin, P" sort="Brundin, P" uniqKey="Brundin P" first="P." last="Brundin">P. Brundin</name><name sortKey="Grasbon Frodl, E M" sort="Grasbon Frodl, E M" uniqKey="Grasbon Frodl E" first="E. M." last="Grasbon-Frodl">E. M. Grasbon-Frodl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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