Gonzalez-Aparicio, RamiroBlanco, EduardoSerrano, AntoniaPavon, Francisco JavierParsons, Loren HMaldonado, RafaelRobledo, PatriciaFernandez-Espejo, EmilioRodríguez de Fonseca, Fernando2015-09-102015-09-102014-03Gonzalez-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):455-681461-1457http://hdl.handle.net/10668/1980Journal Article; Research Support, Non-U.S. Gov't;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.enDopaminergic neuronsNeuroprotectionParkinson's diseasePPARxModelos de enfermedad en animalesRelación dosis-respuesta de medicamentosActividad motoraNeurotoxinasÁcidos oleicosTrastornos parkinsonianosSustancia negraSinaptofisinaMedical Subject Headings::Anatomy::Cells::Cells, CulturedMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Basal Ganglia::Corpus StriatumMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Animal::Disease Models, AnimalMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Dose-Response Relationship, DrugMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Heme Oxygenase (Decyclizing)::Heme Oxygenase-1Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Alcohol Oxidoreductases::Lactate Dehydrogenases::L-Lactate DehydrogenaseMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor ActivityMedical Subject Headings::Anatomy::Nervous System::NeuronsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Neuroprotective AgentsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Noxae::NeurotoxinsMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic AcidsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Catecholamines::Dopamine::Hydroxydopamines::OxidopamineMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian DisordersMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, WistarMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Mesencephalon::Tegmentum Mesencephali::Substantia NigraMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::SynaptophysinMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Tyrosine 3-MonooxygenaseMedical Subject Headings::Organisms::Eukaryotaresearch article24169105open access10.1017/S14611457130012591469-5111