RT Journal Article
T1 The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism.
A1 Gonzalez-Aparicio, Ramiro
A1 Blanco, Eduardo
A1 Serrano, Antonia
A1 Pavon, Francisco Javier
A1 Parsons, Loren H
A1 Maldonado, Rafael
A1 Robledo, Patricia
A1 Fernandez-Espejo, Emilio
A1 Rodríguez de Fonseca, Fernando
K1 Dopaminergic neurons
K1 Neuroprotection
K1 Parkinson's disease
K1 PPARx
K1 Modelos de enfermedad en animales
K1 Relación dosis-respuesta de medicamentos
K1 Actividad motora
K1 Neurotoxinas
K1 Ácidos oleicos
K1 Trastornos parkinsonianos
K1 Sustancia negra
K1 Sinaptofisina
AB 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.
PB Oxford University Press
SN 1461-1457
YR 2014
FD 2014-03
LK http://hdl.handle.net/10668/1980
UL http://hdl.handle.net/10668/1980
LA en
NO Gonzalez-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. Int. J. Neuropsychopharmacol. 2014; 17(3):455-68
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Feb 14, 2025