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The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism

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dc.contributor.author González-Aparicio, Ramiro
dc.contributor.author Blanco, Eduardo
dc.contributor.author Serrano, Antonia
dc.contributor.author Pavón, Francisco Javier
dc.contributor.author Parsons, Loren H.
dc.contributor.author Maldonado, Rafael, 1961-
dc.contributor.author Robledo, Patricia, 1958-
dc.contributor.author Fernández-Espejo, Emilio
dc.contributor.author Rodríguez de Fonseca, Fernando
dc.date.accessioned 2015-06-16T08:18:26Z
dc.date.available 2015-06-16T08:18:26Z
dc.date.issued 2014
dc.identifier.citation González-Aparicio R, Blanco E, Serrano A, Pavon FJ, Parsons LH, Maldonado R et al. The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. International Journal of Neuropsychopharmacology. 2014;17(3):455-68. DOI: 10.1017/S1461145713001259
dc.identifier.issn 1461-457
dc.identifier.uri http://hdl.handle.net/10230/23829
dc.description.abstract Oleoylethanolamide (OEA) is an agonist of the peroxisome proliferator-activated receptor α (PPARα) and has been described to exhibit neuroprotective properties when administered locally in animal models of several neurological disorder models, including stroke and Parkinson's disease. However, there is little information regarding the effectiveness of systemic administration of OEA on Parkinson's disease. In the present study, OEA-mediated neuroprotection has been tested on in vivo and in vitro models of 6-hydroxydopamine (6-OH-DA)-induced degeneration. The in vivo model was based on the intrastriatal infusion of the neurotoxin 6-OH-DA, which generates Parkinsonian symptoms. Rats were treated 2 h before and after the 6-OH-DA treatment with systemic OEA (0.5, 1, and 5 mg/kg). The Parkinsonian symptoms were evaluated at 1 and 4 wk after the development of lesions. The functional status of the nigrostriatal system was studied through tyrosine-hydroxylase (TH) and hemeoxygenase-1 (HO-1, oxidation marker) immunostaining as well as by monitoring the synaptophysin content. In vitro cell cultures were also treated with OEA and 6-OH-DA. As expected, our results revealed 6-OH-DA induced neurotoxicity and behavioural deficits; however, these alterations were less severe in the animals treated with the highest dose of OEA (5 mg/kg). 6-OH-DA administration significantly reduced the striatal TH-immunoreactivity (ir) density, synaptophysin expression, and the number of nigral TH-ir neurons. Moreover, 6-OH-DA enhanced striatal HO-1 content, which was blocked by OEA (5 mg/kg). In vitro, 0.5 and 1 µm of OEA exerted significant neuroprotection on cultured nigral neurons. These effects were abolished after blocking PPARα with the selective antagonist GW6471. In conclusion, systemic OEA protects the nigrostriatal circuit from 6-OH-DA-induced neurotoxicity through a PPARα-dependent mechanism.
dc.description.sponsorship This work was supported by grants to EFE, RM and FRF from Fundació La Marató TV3, and Red de Trastornos Adictivos (Instituto de Salud Carlos III, RD06/0001/0002, RD06/0001/0001, RD06/0001/0005, and FEDER funds) and to EFE from Delegación del Gobierno para el Plan Nacional sobre Drogas (PNSD2009I039) and Junta de Andalucía (BIO127, PAIDI). EB is a recipient of a ‘Marie Curie’ COFUND Fellowship (U-Mobility, number 246550) from the University of Málaga and the 7th Framework Program (FP7). The authors thank Beatriz Galan-Rodriguez, Mara Guerra and Silvia Castellano for animal care and technical assistance, and Juan Luis Ribas (Servicio de Microscopia, CITIUS, University of Seville) for stereological advice
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof International Journal of Neuropsychopharmacology. 2014;17(3):455-68
dc.rights © CINP
dc.subject.other Parkinson, Malaltia de
dc.subject.other Neurones
dc.title The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1017/S1461145713001259
dc.subject.keyword Dopaminergic neurons
dc.subject.keyword 6-hydroxydopamine
dc.subject.keyword Neuroprotection
dc.subject.keyword Parkinson's disease
dc.subject.keyword PPARα
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/246550
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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