Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model.
Animals
Cyclic AMP Response Element-Binding Protein
/ antagonists & inhibitors
Disease Models, Animal
Dyskinesia, Drug-Induced
/ metabolism
Excitatory Amino Acid Antagonists
/ pharmacology
Levodopa
/ toxicity
Male
Oxidopamine
/ toxicity
Protein Interaction Maps
/ drug effects
Random Allocation
Rats
Rats, Wistar
Riluzole
/ pharmacology
6-OHDA-lesioned rats
AIMs
CREB1
Dyskinesia
Riluzole
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
13
07
2018
accepted:
15
11
2018
pubmed:
30
11
2018
medline:
15
1
2020
entrez:
29
11
2018
Statut:
ppublish
Résumé
Chronic administration of L-DOPA, the first-line treatment of dystonic symptoms in childhood or in Parkinson's disease, often leads to the development of abnormal involuntary movements (AIMs), which represent an important clinical problem. Although it is known that Riluzole attenuates L-DOPA-induced AIMs, the molecular mechanisms underlying this effect are not understood. Therefore, we studied the behavior and performed RNA sequencing of the striatum in three groups of rats that all received a unilateral lesion with 6-hydroxydopamine in their medial forebrain bundle, followed by the administration of saline, L-DOPA, or L-DOPA combined with Riluzole. First, we provide evidence that Riluzole attenuates AIMs in this rat model. Subsequently, analysis of the transcriptomics data revealed that Riluzole is predicted to reduce the activity of CREB1, a transcription factor that regulates the expression of multiple proteins that interact in a molecular landscape involved in apoptosis. Although this mechanism underlying the beneficial effect of Riluzole on AIMs needs to be confirmed, it provides clues towards novel or existing compounds for the treatment of AIMs that modulate the activity of CREB1 and, hence, its downstream targets.
Identifiants
pubmed: 30484112
doi: 10.1007/s12035-018-1433-x
pii: 10.1007/s12035-018-1433-x
pmc: PMC6647536
doi:
Substances chimiques
Creb1 protein, rat
0
Cyclic AMP Response Element-Binding Protein
0
Excitatory Amino Acid Antagonists
0
Levodopa
46627O600J
Riluzole
7LJ087RS6F
Oxidopamine
8HW4YBZ748
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5111-5121Subventions
Organisme : FP7-PEOPLE-2012-ITN
ID : 316978
Organisme : FP7-PEOPLE-2012-ITN
ID : 316978
Organisme : FP7-PEOPLE-2012-ITN
ID : 316978
Organisme : Semmelweis Egyetem
ID : ÚNKP-18-4
Organisme : Magyar Tudományos Akadémia (HU)
ID : BO/00987/16/5
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