Publications

Dernière publication 27/08/2014

Inhibition of Adenylyl Cyclase Type 5 Prevents l-DOPA-Induced Dyskinesia in an A

The dopamine precursor l-3,4-dihydroxyphenylalanine (l-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's...

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    [title] => Inhibition of Adenylyl Cyclase Type 5 Prevents l-DOPA-Induced Dyskinesia in an A
    [paragraph] => Inhibition of Adenylyl Cyclase Type 5 Prevents l-DOPA-Induced Dyskinesia in an Animal Model of Parkinson's Disease
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Authors
H.-Y. Park, Y.-M. Kang, Y. Kang, T.-S. Park, Y.-K. Ryu et al.

 Lab
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Journal
The Journal of Neuroscience
Abstract
The dopamine precursor l-3,4-dihydroxyphenylalanine (l-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's disease. However, the long-term use of l-DOPA leads to the development of debilitating involuntary movements, called l-DOPA-induced dyskinesia (LID). The cAMP/protein kinase A (PKA) signaling in the striatum is known to play a role in LID. However, from among the nine known adenylyl cyclases (ACs) present in the striatum, the AC that mediates LID remains unknown. To address this issue, we prepared an animal model with unilateral 6-hydroxydopamine lesions in the substantia nigra in wild-type and AC5-knock-out (KO) mice, and examined behavioral responses to short-term or long-term treatment with l-DOPA. Compared with the behavioral responses of wild-type mice, LID was profoundly reduced in AC5-KO mice. The behavioral protection of long-term treatment with l-DOPA in AC5-KO mice was preceded by a decrease in the phosphorylation levels of PKA substrates ERK (extracellular signal-regulated kinase) 1/2, MSK1 (mitogen- and stress-activated protein kinase 1), and histone H3, levels of which were all increased in the lesioned striatum of wild-type mice. Consistently, FosB/ΔFosB expression, which was induced by long-term l-DOPA treatment in the lesioned striatum, was also decreased in AC5-KO mice. Moreover, suppression of AC5 in the dorsal striatum with lentivirus-shRNA-AC5 was sufficient to attenuate LID, suggesting that the AC5-regulated signaling cascade in the striatum mediates LID. These results identify the AC5/cAMP system in the dorsal striatum as a therapeutic target for the treatment of LID in patients with Parkinson's disease. 
BIOSEB Instruments Used
Grip strength test (BIO-GS3)

Keywords/Topics
Maladie de Parkinson; Neurodégénérescence
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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