Rivera, PatriciaSilva-Peña, DanielBlanco, EduardoVargas, AntonioArrabal, SergioSerrano, AntoniaPavón, Francisco JavierBindila, LauraLutz, BeatRodríguez de Fonseca, FernandoSuárez, Juan2023-01-252023-01-252018-11-26http://hdl.handle.net/10668/13259Previous findings demonstrate a homeostatic role for oleoylethanolamide (OEA) signaling in the ethanol-related neuroinflammation and behavior. However, extensive research is still required in order to unveil the effects of OEA on a number of neurobiological functions such as adult neurogenesis, cell survival and resident neuroimmunity that become notably altered by alcohol. Daily consumption of ethanol (10%) for 2 weeks (6.3 ± 1.1 g/kg/day during last 5 days) caused hypolocomotor activity in rats. This effect appears to rely on central signaling mechanisms given that alcohol increased the OEA levels, the gene expression of OEA-synthesizing enzyme Nape-pld and the number of PPARα-immunoreactive neurons in the striatum. Ethanol-related neurobiological alterations such as a reduction in the number of microglial cells expressing iNOS (a cytokine-inducible immune defense) and in adult neural stem/progenitor cell (NSPC) proliferation (phospho-H3 and BrdU) and maturation (BrdU/β3-tubulin), as well as an increase in damage cell activity (FosB) and apoptosis (cleaved caspase 3) were also observed in the rat striatum. Pharmacological administration of OEA (10 mg/kg) for 5 days during ethanol exposure exacerbated ethanol-induced hypolocomotion and cell apoptosis in the striatum. Interestingly, OEA abrogated the impaired effects of ethanol on PPARα-positive cell population and NSPC proliferation and maturation. OEA also decreased astrocyte-related vimentin immunoreactivity and increased microglial cell population (Iba-1, iNOS) in the striatum. These results suggest that OEA-PPARα signaling modulates glial activation, cell apoptosis and NSPC proliferation and maturation in response to striatal-specific neurobiological alterations induced by prolonged ethanol intake in rats.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/AlcoholLocomotionMicrogliaNeurogenesisPPARαStriatumAlanine TransaminaseAlcohol DrinkingAmidohydrolasesAnimalsApoptosisArachidonic AcidsAspartate AminotransferasesCalcium-Binding ProteinsCaspase 3Cell ProliferationCell SurvivalEndocannabinoidsEthanolEthanolaminesGlial Fibrillary Acidic ProteinHepatobiliary EliminationLocomotionMaleMicrofilament ProteinsMicrogliaNeostriatumNeuronsOleic AcidsPPAR alphaPhospholipase DPolyunsaturated AlkamidesProto-Oncogene Proteins c-fosRatsRats, WistarSignal Transductiongamma-Glutamyltransferaseresearch article30496754open access10.1016/j.neuropharm.2018.11.0371873-7064https://repositori.udl.cat/bitstream/10459.1/67806/7/029329.pdf