Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinson’s disease
| Autor: | Julen Oyarzabal, Victor Echeverry-Alzate, María J. Ramírez, Diana Fernández-Suárez, Marta Celorrio, José Antonio López-Moreno, Cecilia J. Hillard, María S. Aymerich, Rafael Franco, Estefanía Rojo-Bustamante, Rafael Maldonado |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cannabinoid receptor Polyunsaturated Alkamides Immunology Nigrostriatal pathway Arachidonic Acids Pharmacology Biology Amidohydrolases Receptor Cannabinoid CB2 Mice 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Parkinsonian Disorders Receptor Cannabinoid CB1 Fatty acid amide hydrolase Dopamine medicine Animals Parkinson Malaltia de Cannabinoid Receptor Agonists Endocrine and Autonomic Systems URB597 Endocannabinoid system Symptomatic relief Mice Inbred C57BL Monoacylglycerol lipase Disease Models Animal 030104 developmental biology medicine.anatomical_structure Biochemistry chemistry Benzamides Carbamates 030217 neurology & neurosurgery Endocannabinoids medicine.drug |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname |
| ISSN: | 0889-1591 |
| DOI: | 10.1016/j.bbi.2016.06.010 |
| Popis: | Elements of the endocannabinoid system are strongly expressed in the basal ganglia where they suffer profound rearrangements after dopamine depletion. Modulation of the levels of the endocannabinoid 2-arachidonoyl-glycerol by inhibiting monoacylglycerol lipase alters glial phenotypes and provides neuroprotection in a mouse model of Parkinson's disease. In this study, we assessed whether inhibiting fatty acid amide hydrolase could also provide beneficial effects on the time course of this disease. The fatty acid amide hydrolase inhibitor, URB597, was administered chronically to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTPp) over 5weeks. URB597 (1mg/kg) prevented MPTPp induced motor impairment but it did not preserve the dopamine levels in the nigrostriatal pathway or regulate glial cell activation. The symptomatic relief of URB597 was confirmed in haloperidol-induced catalepsy assays, where its anti-cataleptic effects were both blocked by antagonists of the two cannabinoid receptors (CB1 and CB2), and abolished in animals deficient in these receptors. Other fatty acid amide hydrolase inhibitors, JNJ1661010 and TCF2, also had anti-cataleptic properties. Together, these results demonstrate an effect of fatty acid amide hydrolase inhibition on the motor symptoms of Parkinson's disease in two distinct experimental models that is mediated by cannabinoid receptors. This work was supported by the projects PI14/02070 and SAF2012-39875-C02-01 from the Spanish Government (Plan estatal I+D+I 2013–2016 and ISCIII-FEDER), Fundación Gangoiti and the UTE-project/Foundation for Applied Medical Research (FIMA). Estefanía Rojo is supported by a predoctoral fellowship from Colfuturo. Partial support was also provided by the Research and Education Program of the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin |
| Databáze: | OpenAIRE |
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