Disruption of the Microglial ADP Receptor P2Y13 Enhances Adult Hippocampal Neurogenesis

Frontiers in Cellular Neuroscience

Amparo Acker-Palmer¹  Jennifer Stefani²  Olga Tschesnokowa²  Kristine Gampe²  Herbert Zimmermann²  Bernard Robaye³  Jean-Marie Boeynaems³  Marta Parrilla⁴ 

[1] Focus Program Translational Neurosciences (FTN), University of Mainz, Mainz, Germany;Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, Goethe-University, Frankfurt am Main, Germany;Institute of Interdisciplinary Research, School of Medicine, Université Libre de Bruxelles, Bruxelles, Belgium;Max-Planck-Institute for Brain Research, Frankfurt am Main, Germany;

关键词: adult neurogenesis;    ADP;    ATP;    dentate gyrus;    hippocampus;    microglia;   

DOI  :  10.3389/fncel.2018.00134

来源: DOAJ

【 摘 要 】

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 in situ hybridization we show that microglia in brain express the ADP-activated P2Y13 receptor under basal conditions and that P2ry13 mRNA is absent from neurons, astrocytes, and neural progenitor cells. Disrupting P2ry13 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 P2Y13 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 P2Y13R antagonists could boost neurogenesis in pathological conditions associated with impaired hippocampal neurogenesis.

【 授权许可】

Unknown