Reversal of behavioural abnormalities by fetal allografts in a novel rat model of striatonigral degeneration
Identifieur interne : 005582 ( Main/Exploration ); précédent : 005581; suivant : 005583Reversal of behavioural abnormalities by fetal allografts in a novel rat model of striatonigral degeneration
Auteurs : G. K. Wenning [Royaume-Uni] ; R. Granata [Italie] ; P. M. Laboyrie ; N. P. Quinn [Royaume-Uni] ; Jenner ; C. D. Marsden [Royaume-Uni]Source :
- Movement Disorders [ 0885-3185 ] ; 1996-09.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Amphetamines (pharmacology), Animal, Animal model, Animals, Apomorphine (pharmacology), Behavior, Animal (drug effects), Behavioral disorder, Cografts, Corpus Striatum (drug effects), Corpus Striatum (physiopathology), Fetal Tissue Transplantation, Fetus, Graft, Graft Survival, Immunohistochemistry, Male, Mesencephalic transplantation, Mesencephalon (embryology), Mesencephalon (surgery), Midbrain, Multiple system atrophy, Nerve Degeneration, Neuron, Oxidopamine (pharmacology), Quinolinic Acid (pharmacology), Rat, Rat model, Rats, Rats, Wistar, Reversibility, Striatal transplantation, Striatonigral degeneration, Substantia Nigra (drug effects), Substantia Nigra (physiopathology), Transplantation, Homologous, Treatment efficiency.
- MESH :
- chemical , pharmacology : Amphetamines, Apomorphine, Oxidopamine, Quinolinic Acid.
- drug effects : Behavior, Animal, Corpus Striatum, Substantia Nigra.
- embryology : Mesencephalon.
- physiopathology : Corpus Striatum, Substantia Nigra.
- surgery : Mesencephalon.
- Animals, Fetal Tissue Transplantation, Graft Survival, Immunohistochemistry, Male, Nerve Degeneration, Rats, Rats, Wistar, Transplantation, Homologous.
Abstract
We have developed a rodent model of striatonigral degeration, one of the core pathologies underlying the disease multiple system atrophy (MSA). 6‐Hydroxydopamine (6‐OHDA) was administered into the left medial forebrain bundle of male Wistar rats, followed 3–4 weeks later by intrastriatal injection of quinolinic acid into the ipsilateral stratum. The 6‐OHDA lesion resulted in ipsilateral rotation to (+)‐amphetamine and contralateral rotation to apomorphine. Following the subsequent striatal lesion, amphetamine‐induced ipsilateral rotation persisted, but apomorphine‐induced contralateral rotation was reduced or abolished. Subsequently, the lesioned striatum was implanted with fetal CNS allografts consisting of cell suspensions derived from striatal primordium alone or combined with cografts of ventral mesencephalon. Cografted rats showed a reduction or reversal of amphetamine‐induced rotation. This was not observed in animals receiving striatal grafts alone. Apomorphine‐induced contralateral rotation was restored after striatal grafts alone, but only partially in animals receiving sham or cografts. Tyrosine hydroxylase (TH) and dopamine‐ and cyclic adenosine 3′:5′‐monophosphate‐regulated phosphoprotein (DARPP 32) immunocytochemistry showed mesencephalic and striatal graft survival in most animals. However, dopaminergic outgrowth was restricted to the graft deposit. The latter was surrounded by a markedly gliotic glial fibrillary acidic protein‐positive capsule continuous with corpus callosum. Dopaminergic reinnervation of denervated and lesioned adult striatum itself was absent, suggesting that rotational recovery was due to diffuse dopamine release. The study shows that combined unilateral lesioning of rodent medial forebrain bundle and striatum results in a characterstic drug‐induced rotational response that can be partly restored by mesencephalic/striatal cografts.
Url:
DOI: 10.1002/mds.870110507
Affiliations:
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Laboyrie</name><affiliation><wicri:noCountry code="subField">King's College London</wicri:noCountry></affiliation></author><author><name sortKey="Quinn, N P" sort="Quinn, N P" uniqKey="Quinn N" first="N. P." last="Quinn">N. P. Quinn</name><affiliation wicri:level="2"><country>Royaume-Uni</country><placeName><region type="country">Angleterre</region></placeName><wicri:cityArea>Department of Clinical Neurology, Institute of Neurology, London</wicri:cityArea></affiliation></author><author><name sortKey="Jenner" sort="Jenner" uniqKey="Jenner" last="Jenner">Jenner</name><affiliation><wicri:noCountry code="subField">King's College London</wicri:noCountry></affiliation></author><author><name sortKey="Marsden, C D" sort="Marsden, C D" uniqKey="Marsden C" first="C. D." last="Marsden">C. D. Marsden</name><affiliation wicri:level="2"><country>Royaume-Uni</country><placeName><region type="country">Angleterre</region></placeName><wicri:cityArea>Department of Clinical Neurology, Institute of Neurology, London</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="1996-09">1996-09</date><biblScope unit="vol">11</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="522">522</biblScope><biblScope unit="page" to="532">532</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">BAB499812179C3455E3CEE299CA4EF712FB6D36F</idno><idno type="DOI">10.1002/mds.870110507</idno><idno type="ArticleID">MDS870110507</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amphetamines (pharmacology)</term><term>Animal</term><term>Animal model</term><term>Animals</term><term>Apomorphine (pharmacology)</term><term>Behavior, Animal (drug effects)</term><term>Behavioral disorder</term><term>Cografts</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (physiopathology)</term><term>Fetal Tissue Transplantation</term><term>Fetus</term><term>Graft</term><term>Graft Survival</term><term>Immunohistochemistry</term><term>Male</term><term>Mesencephalic transplantation</term><term>Mesencephalon (embryology)</term><term>Mesencephalon (surgery)</term><term>Midbrain</term><term>Multiple system atrophy</term><term>Nerve Degeneration</term><term>Neuron</term><term>Oxidopamine (pharmacology)</term><term>Quinolinic Acid (pharmacology)</term><term>Rat</term><term>Rat model</term><term>Rats</term><term>Rats, Wistar</term><term>Reversibility</term><term>Striatal transplantation</term><term>Striatonigral degeneration</term><term>Substantia Nigra (drug effects)</term><term>Substantia Nigra (physiopathology)</term><term>Transplantation, Homologous</term><term>Treatment efficiency</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amphetamines</term><term>Apomorphine</term><term>Oxidopamine</term><term>Quinolinic Acid</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Behavior, Animal</term><term>Corpus Striatum</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="embryology" xml:lang="en"><term>Mesencephalon</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Corpus Striatum</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Mesencephalon</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Fetal Tissue Transplantation</term><term>Graft Survival</term><term>Immunohistochemistry</term><term>Male</term><term>Nerve Degeneration</term><term>Rats</term><term>Rats, Wistar</term><term>Transplantation, Homologous</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animal</term><term>Atrophie multisystématisée</term><term>Efficacité traitement</term><term>Foetus</term><term>Greffe</term><term>Modèle animal</term><term>Mésencéphale</term><term>Neurone</term><term>Rat</term><term>Réversibilité</term><term>Trouble comportement</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have developed a rodent model of striatonigral degeration, one of the core pathologies underlying the disease multiple system atrophy (MSA). 6‐Hydroxydopamine (6‐OHDA) was administered into the left medial forebrain bundle of male Wistar rats, followed 3–4 weeks later by intrastriatal injection of quinolinic acid into the ipsilateral stratum. The 6‐OHDA lesion resulted in ipsilateral rotation to (+)‐amphetamine and contralateral rotation to apomorphine. Following the subsequent striatal lesion, amphetamine‐induced ipsilateral rotation persisted, but apomorphine‐induced contralateral rotation was reduced or abolished. Subsequently, the lesioned striatum was implanted with fetal CNS allografts consisting of cell suspensions derived from striatal primordium alone or combined with cografts of ventral mesencephalon. Cografted rats showed a reduction or reversal of amphetamine‐induced rotation. This was not observed in animals receiving striatal grafts alone. Apomorphine‐induced contralateral rotation was restored after striatal grafts alone, but only partially in animals receiving sham or cografts. Tyrosine hydroxylase (TH) and dopamine‐ and cyclic adenosine 3′:5′‐monophosphate‐regulated phosphoprotein (DARPP 32) immunocytochemistry showed mesencephalic and striatal graft survival in most animals. However, dopaminergic outgrowth was restricted to the graft deposit. The latter was surrounded by a markedly gliotic glial fibrillary acidic protein‐positive capsule continuous with corpus callosum. Dopaminergic reinnervation of denervated and lesioned adult striatum itself was absent, suggesting that rotational recovery was due to diffuse dopamine release. The study shows that combined unilateral lesioning of rodent medial forebrain bundle and striatum results in a characterstic drug‐induced rotational response that can be partly restored by mesencephalic/striatal cografts.</div></front></TEI><affiliations><list><country><li>Italie</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Latium</li></region><settlement><li>Rome</li></settlement></list><tree><noCountry><name sortKey="Jenner" sort="Jenner" uniqKey="Jenner" last="Jenner">Jenner</name><name sortKey="Laboyrie, P M" sort="Laboyrie, P M" uniqKey="Laboyrie P" first="P. M." last="Laboyrie">P. M. Laboyrie</name></noCountry><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Wenning, G K" sort="Wenning, G K" uniqKey="Wenning G" first="G. K." last="Wenning">G. K. Wenning</name></region><name sortKey="Marsden, C D" sort="Marsden, C D" uniqKey="Marsden C" first="C. D." last="Marsden">C. D. Marsden</name><name sortKey="Quinn, N P" sort="Quinn, N P" uniqKey="Quinn N" first="N. P." last="Quinn">N. P. Quinn</name></country><country name="Italie"><region name="Latium"><name sortKey="Granata, R" sort="Granata, R" uniqKey="Granata R" first="R." last="Granata">R. Granata</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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