2026-07-22T20:10:08Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/170872024-11-28T14:57:37Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Sayd, Aline author Antón, María author Alén, Francisco author Caso, Javier Rubén author Pavón, Francisco-Javier author Leza, Juan Carlos author Rodríguez de Fonseca, Fernando author García-Bueno, Borja author Orio, Laura authoraffiliation [Anton,M; Alen,F; Rodríguez de Fonseca,F; Orio,L] Department of Psychobiology, Faculty of Psychology, Complutense University, Complutense University of Madrid (UCM), Madrid, Spain. [Said,A; Lez,JC; Garcia-Bueno,B] Department of Pharmacology, Faculty of Medicine, UCM, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)), Madrid, Spain . [Caso,JR] Department of Psychiatry, Faculty of Medicine, UCM, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain. [Pavón,J; Rodriguez de Fonseca,F] UGC Salud Mental. Instituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de Málaga.Universidad de Málaga. Red de Trastornos Adictivos, Málaga, Spain. 2024-01-15T18:17:35Z 2024-01-15T18:17:35Z 2015-04 10.1093/ijnp/pyu111 1469-5111 1461-1457 The International Journal of Neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) http://hdl.handle.net/10668/2337 25548106 http://hdl.handle.net/20.500.12105/17087 BACKGROUND: The acylethanolamides oleoylethanolamide and palmitoylethanolamide are endogenous lipid mediators with proposed neuroprotectant properties in central nervous system (CNS) pathologies. The precise mechanisms remain partly unknown, but growing evidence suggests an antiinflammatory/antioxidant profile. METHODS: We tested whether oleoylethanolamide/palmitoylethanolamide (10 mg/kg, i.p.) attenuate neuroinflammation and acute phase responses (hypothalamus-pituitary-adrenal (HPA) stress axis stress axis activation, thermoregulation, and anhedonia) induced by lipopolysaccharide (0.5 mg/kg, i.p.) in rats. RESULTS: Lipopolysaccharide increased mRNA levels of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6, nuclear transcription factor-κB activity, and the expression of its inhibitory protein IκBα in cytoplasm, the inducible isoforms of nitric oxide synthase and cyclooxygenase-2, microsomal prostaglandin E2 synthase mRNA, and proinflammatory prostaglandin E2 content in frontal cortex 150 minutes after administration. As a result, the markers of nitrosative/oxidative stress nitrites (NO2(-)) and malondialdehyde were increased. Pretreatment with oleoylethanolamide/ palmitoylethanolamide reduced plasma tumor necrosis factor-α levels after lipopolysaccharide, but only oleoylethanolamide significantly reduced brain tumor necrosis factor-α mRNA. Oleoylethanolamide and palmitoylethanolamide prevented lipopolysaccharide-induced nuclear transcription factor-κB (NF-κB)/IκBα upregulation in nuclear and cytosolic extracts, respectively, the expression of inducible isoforms of nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E2 synthase and the levels of prostaglandin E2. Additionally, both acylethanolamides reduced lipopolysaccharide-induced oxidative/nitrosative stress. Neither oleoylethanolamide nor palmitoylethanolamide modified plasma corticosterone levels after lipopolysaccharide, but both acylethanolamides reduced the expression of hypothalamic markers of thermoregulation interleukin-1β, cyclooxygenase-2, and prostaglandin E2, and potentiated the hypothermic response after lipopolysaccharide. Interestingly, only oleoylethanolamide disrupted lipopolysaccharide-induced anhedonia in a saccharine preference test. CONCLUSIONS: Results indicate that oleoylethanolamide and palmitoylethanolamide have antiinflammatory/neuroprotective properties and suggest a role for these acylethanolamides as modulators of CNS pathologies with a neuroinflammatory component. eng OLEA Lipopolysaccharide Neuroinflammation Anhedonia Antiinflamatorios Corticosterona Citocinas Modelos de enfermedad en animales Encefalitis Endocannabinoides Endotoxinas Etanolaminas PEA Preferencias alimenticias Lóbulo frontal Sistema hipotálamo-hipofisario Mediadores de la inflamación Peroxidación de lípidos Fármacos neuroprotectores Ácidos oleicos Estrés oxidativo Ácidos palmíticos Sistema hipófiso-suprarrenal Ratas wistar Percepción del gusto Systemic administration of oleoylethanolamide protects from neuroinflammation and anhedonia induced by LPS in rats. research article