ParkinsonCanadaV1, Main, Exploration, bibRecord, 002107

Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat model of Parkinson's : an in vivo imaging study

Identifieur interne : 002107 ( Main/Exploration ); précédent : 002106; suivant : 002108

Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat model of Parkinson's : an in vivo imaging study

Auteurs : Vesna Sossi [Canada] ; Katherine Dinelle [Canada] ; Geoffrey J. Topping [Canada] ; James E. Holden [États-Unis] ; Doris Doudet [Canada] ; Michael Schulzer [Canada] ; Thomas J. Ruth [Canada] ; A. Jon Stoessl [Canada] ; Raul De La Fuente-Femandez [Canada]

Source :

Journal of neurochemistry [ 0022-3042 ] ; 2009.

RBID : Pascal:09-0155749

Descripteurs français

Pascal (Inist)
- Dopamine, Lévodopa, Modèle animal, Enervation, Lésion, Récepteur dopaminergique D2, Oscillation, Cinétique, Maladie de Parkinson, Positon, Tomoscintigraphie, Dyskinésie, Rat, Homme.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Animal model, D2 Dopamine receptor, Denervation, Dopamine, Dyskinesia, Emission tomography, Human, Kinetics, Lesion, Levodopa, Oscillation, Parkinson disease, Positron, Rat.

Abstract

Studies showed that the dopamine (DA) transporter (DAT) modulates changes in levodopa-derived synaptic dopamine levels (A(DA)) in Parkinson's disease (PD). Here we evaluate the relationship between DAT and A(DA) in the 6-hydroxy-dopamine model of Parkinson's disease to investigate these mechanisms as a function of dopaminergic denervation and in relation to other denervation-induced regulatory changes. 27 rats with a unilateral 6-hydroxydopamine lesion (denervation ∼20-97%) were imaged with ¹¹C-dihydrotetrabenazine (VMAT2 marker), ¹¹C-methylphenidate (DAT marker) and ¹¹C-raclopride (D2-type receptor marker). For denervation <75% A(DA) was significantly correlated with a combination of relatively preserved terminal density and lower DAT. For denervation <90%, A(DA) was significantly negatively correlated with DAT with a weaker dependence on VMAT2. For the entire data set, no dependence on pre-synaptic markers was observed; A(DA) was significantly positively correlated with ¹¹C-raclopride binding-derived estimates of DA loss. These findings parallel observations in humans, and show that (i) regulatory changes attempt to normalize synaptic DA levels (ii) a lesion-induced functional dependence of A(DA) on DAT occurs up to ∼ 90% denervation (iii) for denervation < 75% relative lower DAT levels may relate to effective compensation; for higher denervation, lower DAT levels likely contribute to oscillations in synaptic DA associated with dyskinesias.

Affiliations:

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Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal model</term>
<term>D2 Dopamine receptor</term>
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<term>Dopamine</term>
<term>Dyskinesia</term>
<term>Emission tomography</term>
<term>Human</term>
<term>Kinetics</term>
<term>Lesion</term>
<term>Levodopa</term>
<term>Oscillation</term>
<term>Parkinson disease</term>
<term>Positron</term>
<term>Rat</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Dopamine</term>
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<term>Modèle animal</term>
<term>Enervation</term>
<term>Lésion</term>
<term>Récepteur dopaminergique D2</term>
<term>Oscillation</term>
<term>Cinétique</term>
<term>Maladie de Parkinson</term>
<term>Positon</term>
<term>Tomoscintigraphie</term>
<term>Dyskinésie</term>
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<front><div type="abstract" xml:lang="en">Studies showed that the dopamine (DA) transporter (DAT) modulates changes in levodopa-derived synaptic dopamine levels (A(DA)) in Parkinson's disease (PD). Here we evaluate the relationship between DAT and A(DA) in the 6-hydroxy-dopamine model of Parkinson's disease to investigate these mechanisms as a function of dopaminergic denervation and in relation to other denervation-induced regulatory changes. 27 rats with a unilateral 6-hydroxydopamine lesion (denervation ∼20-97%) were imaged with <sup>11</sup>
C-dihydrotetrabenazine (VMAT2 marker), <sup>11</sup>
C-methylphenidate (DAT marker) and <sup>11</sup>
C-raclopride (D2-type receptor marker). For denervation <75% A(DA) was significantly correlated with a combination of relatively preserved terminal density and lower DAT. For denervation <90%, A(DA) was significantly negatively correlated with DAT with a weaker dependence on VMAT2. For the entire data set, no dependence on pre-synaptic markers was observed; A(DA) was significantly positively correlated with <sup>11</sup>
C-raclopride binding-derived estimates of DA loss. These findings parallel observations in humans, and show that (i) regulatory changes attempt to normalize synaptic DA levels (ii) a lesion-induced functional dependence of A(DA) on DAT occurs up to ∼ 90% denervation (iii) for denervation < 75% relative lower DAT levels may relate to effective compensation; for higher denervation, lower DAT levels likely contribute to oscillations in synaptic DA associated with dyskinesias.</div>
</front>
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<name sortKey="De La Fuente Femandez, Raul" sort="De La Fuente Femandez, Raul" uniqKey="De La Fuente Femandez R" first="Raul" last="De La Fuente-Femandez">Raul De La Fuente-Femandez</name>
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<country name="États-Unis"><region name="Wisconsin"><name sortKey="Holden, James E" sort="Holden, James E" uniqKey="Holden J" first="James E." last="Holden">James E. Holden</name>
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	La maladie de Parkinson au Canada (serveur d'exploration)
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La maladie de Parkinson au Canada (serveur d'exploration)

Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat model of Parkinson's : an in vivo imaging study

Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat model of Parkinson's : an in vivo imaging study

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Abstract

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Le document en format XML

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Pour mettre un lien sur cette page dans le réseau Wicri