AUTHOR=Stefani Jennifer , Tschesnokowa Olga , Parrilla Marta , Robaye Bernard , Boeynaems Jean-Marie , Acker-Palmer Amparo , Zimmermann Herbert , Gampe Kristine 

TITLE=Disruption of the Microglial ADP Receptor P2Y13 Enhances Adult Hippocampal Neurogenesis

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=12

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2018.00134

DOI=10.3389/fncel.2018.00134

ISSN=1662-5102

ABSTRACT=<p>In mammalian species, including humans, the hippocampal dentate gyrus (DG) is a primary region of adult neurogenesis. Aberrant adult hippocampal neurogenesis is associated with neurological pathologies. Understanding the cellular mechanisms controlling adult hippocampal neurogenesis is expected to open new therapeutic strategies for mental disorders. Microglia is intimately associated with neural progenitor cells in the hippocampal DG and has been implicated, under varying experimental conditions, in the control of the proliferation, differentiation and survival of neural precursor cells. But the underlying mechanisms remain poorly defined. Using fluorescent <italic>in situ</italic> hybridization we show that microglia in brain express the ADP-activated P2Y<sub>13</sub> receptor under basal conditions and that <italic>P2ry13</italic> mRNA is absent from neurons, astrocytes, and neural progenitor cells. Disrupting <italic>P2ry13</italic> decreases structural complexity of microglia in the hippocampal subgranular zone (SGZ). But it increases progenitor cell proliferation and new neuron formation. Our data suggest that P2Y<sub>13</sub> receptor-activated microglia constitutively attenuate hippocampal neurogenesis. This identifies a signaling pathway whereby microglia, via a nucleotide-mediated mechanism, contribute to the homeostatic control of adult hippocampal neurogenesis. Selective P2Y<sub>13</sub>R antagonists could boost neurogenesis in pathological conditions associated with impaired hippocampal neurogenesis.</p>