Anales RANF

P.58 ADENOSINE A 2A RECEPTOR ANTAGONISTS POTENTIATE CANNABINOID SIGNALING IN MICROGLIA Rafael Franco 1,2 , Irene Reyes 1,2 , David Aguinaga 1,2 , Alejandro Lillo 1 , Jasmina Jiménez 1,2 , Iu Raïch 1 , Dasiel O. Borroto-Escuela 3 , Carlos Ferreiro-Vera 4 , Enric I. Canela 1,2 , Verónica Sánchez de Medina 4 , Anna del Ser-Badia 2,5 , Kjell Fuxe 3 , Carlos A. Saura 2,5 and Gemma Navarro 2,6 1 . Molecular Neurobiology laboratory, Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona. Barcelona. Spain; 2. Centro de Investigación en Red, Enfermedades Neurodegenerativas (CIBERNED). Instituto de Salud Carlos III. Madrid. Spain; 3. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; 4 . Phytoplant Research S.L., Córdoba, Spain; 5 . Institut de Neurociències, Department de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra. Barcelona, Spain; 6 . Dept. Biochemistry and Molecular Biology. Faculty of Pharmacy and Food Sciences. Universitat de Barcelona. Barcelona. Spain. Neuroprotective M 2 -skewed microglia appear as promising to alter the course of neurodegenerative diseases and G-protein-coupled receptors are potential targets to achieve such microglial polarization. A common feature of adenosine A2A and cannabinoid CB 2 receptors in microglia is that their expression is upregulated in Alzheimer’s disease (AD). We here show a close interrelationship between those receptors in microglia that are able to physically interact and affect the signaling of each other doe to allosteric interaction within an A 2A -CB 2 receptor heteromer (A 2A -CB 2 Het). Particularly relevant is the increase in expression in samples from the APPSw,Ind AD transgenic model. The most relevant finding, confirmed in both heterologous cells and in primary cultures of microglia, was that blockade to A2A receptors resulted in increased CB 2 R-mediated signaling. This heteromer-specific feature suggests that A 2A R antagonists would potentiate, via microglia, the neuroprotective action of endocannabinoids with important implications for an AD therapy.