Pharmacological blockade of fatty acid amide hydrolase (FAAH) by URB597 improves memory and changes the phenotype of hippocampal microglia despite ethanol exposure
Fernández Arjona, María del Mar
Silva Peña, Daniel
López Ávalos, María Dolores
Grondona, Jesús M.
Pavón, Francisco Javier
Rodríguez de Fonseca, Fernando
MetadataShow full item record
Changes in endogenous cannabinoid homeostasis are associated with both ethanol-related neuroinflammation and memory decline. Extensive research is still required to unveil the role of endocannabinoid signaling activation on hippocampal microglial cells after ethanol exposure. Either microglial morphology, phenotype and recruitment may become notably altered after chronic alcohol-related neurodegeneration. Here, we evaluated the pharmacological effects of fatty-acid amide-hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg), oleoylethanolamide (OEA, 10 mg/kg), arachidonoylethanolamide (AEA, 10 mg/kg), the CB1 receptor agonist ACEA (3 mg/kg) and the CB2 receptor agonist JWH133 (0.2 mg/kg) administered for 5 days in a rat model of subchronic (2 weeks) ethanol diet (11% v/v) exposure. URB597 turned to be the most effective treatment. URB597 increased microglial (IBA-1+) cell population, and changed morphometric features (cell area and perimeter, roughness, fractal dimension, lacunarity) associated with activated microglia in the hippocampus of ethanol-exposed rats. Regarding innate immune activity, URB597 specifically increased mRNA levels of toll-like receptor 4 (TLR4), glial fibrillary acidic protein (Gfap) and the chemokine stromal cell-derived factor 1 (SDF-1α/CXCL12), and elevated the cell population expressing the chemokine receptors CX3CR1, CCR2 and CCR4 in the ethanol-exposed rat hippocampus. Contrary to ethanol effect, URB597 reduced mRNA levels of Iba-1, Tnfα, IL-6 and the monocyte chemoattractant protein-1 (MCP-1/CCL2), as well as cell population expressing iNOS. URB597 effects on hippocampal immune system were accompanied by changes in short and long-term visual recognition memory. These results suggest that FAAH inhibition may modulates hippocampal microglial recruitment and activation that can be associated with improved hippocampal-dependent memory despite ethanol exposure.
Is part ofBiochemical Pharmacology, 2018, vol. 157, p. 244-257
European research projects
The following license files are associated with this item:
Showing items related by title, author, creator and subject.
Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat Blanco Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodríguez de Fonseca, Fernando (Frontiers Media S.A., 2014-01-08)Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated ...
Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum Rivera, Patricia; Silva Peña, Daniel; Blanco Calvo, Eduardo; Vargas, Antonio; Arrabal, Sergio; Serrano, Antonia; Pavón, Francisco Javier; Bindila, Laura; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan (Elsevier, 2019-03-01)Previous 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 ...
Diet-dependent modulation of hippocampal expression of endocannabinoid signaling-related proteins in cannabinoid antagonist-treated obese rats Rivera, Patricia; Luque-Rojas, María Jesús; Pastor, Antoni; Blanco Calvo, Eduardo; Pavón, Francisco Javier; Serrano, Antonia; Crespillo, Ana; Vida, Margarita; Grondona, Jesús M.; Cifuentes, Manuel; Bermúdez-Silva, Francisco J.; De la Torre, Rafael; Rodríguez de Fonseca, Fernando; Suárez, Juan (Federation of European Neuroscience Societies and John Wiley & Sons, 2013-01-00)Diet-induced obesity produces changes in endocannabinoid signaling (ECS), influencing the regulation of energy homeostasis. Recently, we demonstrated that, in high-fat-diet-fed rats, blockade of CB1 receptor by AM251 not ...