A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery
Identifieur interne : 000F11 ( Main/Exploration ); précédent : 000F10; suivant : 000F12A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery
Auteurs : Stéphanie Mounayar [France] ; Sabrina Boulet [France] ; Dominique Tandé [France] ; Caroline Jan [France] ; Mathias Pessiglione [France] ; Etienne C. Hirsch [France] ; Jean Féger [France] ; Marc Savasta [France] ; Chantal François [France] ; Léon Tremblay [France]Source :
- Brain [ 0006-8950 ] ; 2007-11.
Abstract
The cardinal symptoms in Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine is decreased by 60–80%. During the preclinical phase of PD, compensatory mechanisms are probably involved in delaying the appearance of motor symptoms. In a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of PD, a spontaneous recovery has been reported after initial intoxication suggesting that compensatory mechanisms are activated in this model as well. Assuming that mechanisms are similar in these phenomena, the study of recovery in monkeys following MPTP intoxication may enable identification of compensatory mechanisms involved in the preclinical phase of PD. In order to maximize the temporal similarity between PD and the MPTP model, we assessed a new progressive monkey model in which spontaneous recovery is expressed systematically and to characterize it based on (1) its behavioural features, and (2) the presence of compensatory mechanisms revealed by an immunohistological approach comparing dopaminergic and serotoninergic innervation between monkeys either exhibiting behavioural recovery or stable motor symptoms. This immunohistological study focused on the substantia nigra, striatum and pallidum, and their anatomical and functional subdivisions: sensorimotor, associative and limbic. The behavioural analysis revealed that with progressive MPTP intoxication motor symptoms were initially expressed in all monkeys. Observable recovery from these symptoms occurred in all monkeys (7/7) within 3–5 weeks after the last MPTP injection, and most exhibited a full recovery. In contrast, acute intoxication induced stable motor symptoms. Despite this obvious behavioural difference, immunohistological methods revealed that the loss of dopaminergic cell bodies in substantia nigra was substantial and similar in both MPTP-treated groups. However, quantification of fibres revealed that recovered monkeys displayed more dopaminergic and serotoninergic fibres than those with stable motor symptoms in sensorimotor and associative territories of striatum and more dopaminergic fibres in internal pallidum. This study provides a new model of PD where all monkeys expressed functional recovery from motor symptoms despite a large dopaminergic neuronal loss. The immunohistological results suggest that both dopamine and serotonin could be implicated in the compensatory mechanisms.
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DOI: 10.1093/brain/awm208
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Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris F-75013, Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043, Cedex 09, Université Joseph Fourier, 38041 Grenoble F- 38041, Cedex 09 and Centre Hospitalier Universitaire de Grenoble, Grenoble F-38043, Cedex 09</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 09</settlement></placeName></affiliation></author><author><name sortKey="Jan, Caroline" sort="Jan, Caroline" uniqKey="Jan C" first="Caroline" last="Jan">Caroline Jan</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 679, Paris F-75013, Université Pierre et Marie Curie-Paris6, Institut Fédératif de Recherche de Neurosciences Unité Mixte de Recherche S679, Paris F-75013, Assistance Publique - 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Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris F-75013, Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043, Cedex 09, Université Joseph Fourier, 38041 Grenoble F- 38041, Cedex 09 and Centre Hospitalier Universitaire de Grenoble, Grenoble F-38043, Cedex 09</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 09</settlement></placeName></affiliation></author><author><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 679, Paris F-75013, Université Pierre et Marie Curie-Paris6, Institut Fédératif de Recherche de Neurosciences Unité Mixte de Recherche S679, Paris F-75013, Assistance Publique - Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris F-75013, Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043, Cedex 09, Université Joseph Fourier, 38041 Grenoble F- 38041, Cedex 09 and Centre Hospitalier Universitaire de Grenoble, Grenoble F-38043, Cedex 09</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 09</settlement></placeName></affiliation></author><author><name sortKey="Francois, Chantal" sort="Francois, Chantal" uniqKey="Francois C" first="Chantal" last="François">Chantal François</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 679, Paris F-75013, Université Pierre et Marie Curie-Paris6, Institut Fédératif de Recherche de Neurosciences Unité Mixte de Recherche S679, Paris F-75013, Assistance Publique - Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris F-75013, Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043, Cedex 09, Université Joseph Fourier, 38041 Grenoble F- 38041, Cedex 09 and Centre Hospitalier Universitaire de Grenoble, Grenoble F-38043, Cedex 09</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 09</settlement></placeName></affiliation></author><author><name sortKey="Tremblay, Leon" sort="Tremblay, Leon" uniqKey="Tremblay L" first="Léon" last="Tremblay">Léon Tremblay</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 679, Paris F-75013, Université Pierre et Marie Curie-Paris6, Institut Fédératif de Recherche de Neurosciences Unité Mixte de Recherche S679, Paris F-75013, Assistance Publique - Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris F-75013, Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043, Cedex 09, Université Joseph Fourier, 38041 Grenoble F- 38041, Cedex 09 and Centre Hospitalier Universitaire de Grenoble, Grenoble F-38043, Cedex 09</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 09</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2007-11">2007-11</date><biblScope unit="volume">130</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="2898">2898</biblScope><biblScope unit="page" to="2914">2914</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">1057C84BA24C1DAF26BA2FBD887E621C091192D3</idno><idno type="DOI">10.1093/brain/awm208</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">The cardinal symptoms in Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine is decreased by 60–80%. During the preclinical phase of PD, compensatory mechanisms are probably involved in delaying the appearance of motor symptoms. In a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of PD, a spontaneous recovery has been reported after initial intoxication suggesting that compensatory mechanisms are activated in this model as well. Assuming that mechanisms are similar in these phenomena, the study of recovery in monkeys following MPTP intoxication may enable identification of compensatory mechanisms involved in the preclinical phase of PD. In order to maximize the temporal similarity between PD and the MPTP model, we assessed a new progressive monkey model in which spontaneous recovery is expressed systematically and to characterize it based on (1) its behavioural features, and (2) the presence of compensatory mechanisms revealed by an immunohistological approach comparing dopaminergic and serotoninergic innervation between monkeys either exhibiting behavioural recovery or stable motor symptoms. This immunohistological study focused on the substantia nigra, striatum and pallidum, and their anatomical and functional subdivisions: sensorimotor, associative and limbic. The behavioural analysis revealed that with progressive MPTP intoxication motor symptoms were initially expressed in all monkeys. Observable recovery from these symptoms occurred in all monkeys (7/7) within 3–5 weeks after the last MPTP injection, and most exhibited a full recovery. In contrast, acute intoxication induced stable motor symptoms. Despite this obvious behavioural difference, immunohistological methods revealed that the loss of dopaminergic cell bodies in substantia nigra was substantial and similar in both MPTP-treated groups. However, quantification of fibres revealed that recovered monkeys displayed more dopaminergic and serotoninergic fibres than those with stable motor symptoms in sensorimotor and associative territories of striatum and more dopaminergic fibres in internal pallidum. This study provides a new model of PD where all monkeys expressed functional recovery from motor symptoms despite a large dopaminergic neuronal loss. The immunohistological results suggest that both dopamine and serotonin could be implicated in the compensatory mechanisms.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Rhône-Alpes</li></region><settlement><li>Cedex 09</li></settlement></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Mounayar, Stephanie" sort="Mounayar, Stephanie" uniqKey="Mounayar S" first="Stéphanie" last="Mounayar">Stéphanie Mounayar</name></region><name sortKey="Boulet, Sabrina" sort="Boulet, Sabrina" uniqKey="Boulet S" first="Sabrina" last="Boulet">Sabrina Boulet</name><name sortKey="Feger, Jean" sort="Feger, Jean" uniqKey="Feger J" first="Jean" last="Féger">Jean Féger</name><name sortKey="Francois, Chantal" sort="Francois, Chantal" uniqKey="Francois C" first="Chantal" last="François">Chantal François</name><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><name sortKey="Jan, Caroline" sort="Jan, Caroline" uniqKey="Jan C" first="Caroline" last="Jan">Caroline Jan</name><name sortKey="Pessiglione, Mathias" sort="Pessiglione, Mathias" uniqKey="Pessiglione M" first="Mathias" last="Pessiglione">Mathias Pessiglione</name><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name><name sortKey="Tande, Dominique" sort="Tande, Dominique" uniqKey="Tande D" first="Dominique" last="Tandé">Dominique Tandé</name><name sortKey="Tremblay, Leon" sort="Tremblay, Leon" uniqKey="Tremblay L" first="Léon" last="Tremblay">Léon Tremblay</name><name sortKey="Tremblay, Leon" sort="Tremblay, Leon" uniqKey="Tremblay L" first="Léon" last="Tremblay">Léon Tremblay</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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