| Přispěvatelé: |
[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., This research was supported by The Spanish Ministry of Health and Social Policy (PNSD, PR29/11-18295 to L.O.), the Regional Government of Madrid (S2011/BMD-2308. CANNAB to JC.L.), Universidad Complutense-Santander (2878–920140 to J.C.L.), and Consejería de Salud y Bienestar Social, Junta Andalucía (PI0228-2013). B.G.-B. is a Ramón y Cajal postdoctoral fellow (Spanish Ministry of Education and Science). |
| Popis: |
Comparative Study; Journal Article; Research Support, Non-U.S. Gov't;Erratium: http://ijnp.oxfordjournals.org/content/19/3/pyw004.long 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. Yes |
