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Title: The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism.
Authors: Gonzalez-Aparicio, Ramiro
Blanco, Eduardo
Serrano, Antonia
Pavon, Francisco Javier
Parsons, Loren H
Maldonado, Rafael
Robledo, Patricia
Fernandez-Espejo, Emilio
Rodríguez de Fonseca, Fernando
metadata.dc.contributor.authoraffiliation: [Gonzalez-Aparicio,R; Fernandez-Espejo,E; Rodríguez de Fonseca,F] Instituto Cajal (CSIC), Madrid, Spain. [Gonzalez-Aparicio,R] Laboratorio de Neurología Molecular y Neurofisiología, Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain. [Blanco,E; Serrano,A; Pavon,FJ; Rodríguez de Fonseca,F] Laboratorio de Medicina Regenerativa, IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Blanco,E]] Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Universidad de Málaga, Málaga, Spain. [Serrano,A; Pavon,FJ; Parsons,LH] Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, California, USA. Maldonado,R; Robledo,P] Laboratorio de Neurofarmacología, Department de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Keywords: Dopaminergic neurons;Neuroprotection;Parkinson's disease;PPARx;Modelos de enfermedad en animales;Relación dosis-respuesta de medicamentos;Actividad motora;Neurotoxinas;Ácidos oleicos;Trastornos parkinsonianos;Sustancia negra;Sinaptofisina
metadata.dc.subject.mesh: Medical Subject Headings::Anatomy::Cells::Cells, Cultured
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Basal Ganglia::Corpus Striatum
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Animal::Disease Models, Animal
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Dose-Response Relationship, Drug
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Heme Oxygenase (Decyclizing)::Heme Oxygenase-1
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Alcohol Oxidoreductases::Lactate Dehydrogenases::L-Lactate Dehydrogenase
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity
Medical Subject Headings::Anatomy::Nervous System::Neurons
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Neuroprotective Agents
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Noxae::Neurotoxins
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic Acids
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Catecholamines::Dopamine::Hydroxydopamines::Oxidopamine
Medical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Wistar
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Mesencephalon::Tegmentum Mesencephali::Substantia Nigra
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Synaptophysin
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Tyrosine 3-Monooxygenase
Medical Subject Headings::Organisms::Eukaryota
Issue Date: Mar-2014
Publisher: Oxford University Press
Citation: 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
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.
Description: Journal Article; Research Support, Non-U.S. Gov't;
metadata.dc.identifier.doi: 10.1017/S1461145713001259
ISSN: 1469-5111 (Online)
1461-1457 (Print)
Appears in Collections:01- Artículos - Hospital Regional de Málaga
01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga

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