Anales RANF

P.64 THE ADP RECEPTOR P2Y 13 IS SELECTIVELY EXPRESSED IN BRAIN MICROGLIA AND CONSTITUTIVELY ATTENUATES HIPPOCAMPAL NEUROGENESIS O. Tschesnokowa 1 , J. Stefani 1 , M. Parilla 1 , K. Gampe 1 , B. Robaye 2 , J.M. Boeynaems 2 , A. Acker-Palmer 1 , H. Zimmermann 1 1 Goethe-University, Frankfurt am Main, Germany 2 Université Libre de Bruxelles, Belgium Brain microglia represent a highly dynamic cell type involved in multiple functions in the CNS. They are involved in both physiological and pathological mechanisms and have been implicated in several neurodegenerative diseases. Purinergic mechanisms play an important role in the control of microglial function. [1] Nucleotide receptors expressed by microglia in situ include the ATP-activated P2X7 and P2X4 receptors, which are strongly upregulated under diverse pathological conditions, the Gq-coupled and UDP-activated P2Y 6 receptor, which has been implicated in microglial phagocytosis as well as three closely related Gi-coupled receptors, the UDP- glucose/UDP-activated P2Y 14 receptor, the ADP-activated receptors P2Y 12 and - in spinal cord microglia - P2Y 13 . These are upregulated in the spinal cord under conditions of neuropathic pain. Using a combination of fluorescent in situ hybridization and immunostaining we allocate the P2Y 13 receptor specifically to brain microglia in situ. Since microglia is situated in close proximity to hippocampal neural progenitor cells and since we have previously demonstrated that purinergic mechanisms are involved in the control of adult neurogenesis [2,3] , we investigated the impact of the P2Y 13 receptor in adult hippocampal neurogenesis using P2ry13 null mice [4] . Disruption of P2ry13 increased hippocampal progenitor cell proliferation and numbers, new neuron formation, and activity of mature granule cells. We have previously shown that the neurogenic niche has the potential to generate the P2Y 13 receptor agonist ADP from extracellular ATP by ectonucleotidases, which are associated with microglia itself, with type 1 cells and neural progenitor cells [3,5,6] . This identifies a novel signaling pathway whereby microglia, via a P2Y 13 receptor-mediated mechanism contribute to the homeostatic control of adult hippocampal neurogenesis. [1 ] Calovi S. et al. (2018) Neuroscience (2018) doi: 10.1016/j.neuroscience.2018.12.021; [2] Zimmermann H. (2011) Semin Cell Dev Biol 22: 194-204; [3] Gampe K. et al. (2015) Stem Cells 33:253-264; [4] Stefani et al. (2018) Front Cell Neurosci 12:134. doi: 10.3389/fncel. 2018.00134; [5] Braun N. et al (1998) J Neurosci 18:4891-900; [6] Braun et al. (2000) Eur J Neurosci 12: 4357-4366