Browsing by Author "Koester, Erin C."
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Item Endocannabinoid regulation of amyloid-induced neuroinflammation(Neurobiology of Aging, 2015) Vázquez, Carmen; Tolón, Rosa María; Grande Rodríguez, Mª Teresa; Caraza, Marina; Moreno, Marta; Koester, Erin C.; Villaescusa, Borja; Ruiz Valdepeñas, Lourdes; Fernández Sánchez, Francisco Javier; Cravatt, Benjamin F.; Hillard, Cecilia J.; Romero, JuliánThe modulation of endocannabinoid (EC) levels and the activation of cannabinoid receptors are seen as promising therapeutic strategies in a variety of diseases, including Alzheimer’s disease (AD). We aimed to evaluate the effect of the pharmacological and genetic inhibiton of anandamide (AEA)-degrading enzyme in a mouse model of AD (5xFAD). Pharmacological inhibition of the fatty acid amide hydrolase (FAAH) had little impact on the expression of key enzymes and cytokines as well as on the cognitive impairment and plaque deposition and gliosis in 5xFAD mice. CB1 blockade exacerbated inflammation in this transgenic mouse model of AD. The genetic inactivation of FAAH led to increases in the expression of inflammatory cytokines. At the same time, FAAH-null 5xFAD mice exhibited a behavioral improvement in spatial memory that was independent of the level of anxiety and was not CB1-mediated. Finally, mice lacking FAAH showed diminished soluble amyloid levels, neuritic plaques and gliosis. These data reinforce the notion of a role for the endocannabinoid system in neuroinflammation and open new perspectives on the relevance of modulating endocannabinoid levels in the inflammed brain.