TY  - JOUR
A1  - Stefani, Jennifer
A1  - Tschesnokowa, Olga
A1  - Parrilla, Marta
A1  - Robaye, Bernard
A1  - Boeynaems, Jean-Marie
A1  - Acker-Palmer, Amparo
A1  - Zimmermann, Herbert
A1  - Gampe, Kristine
T1  - Disruption of the microglial ADP receptor P2Y13 enhances adult hippocampal neurogenesis
T2  - Frontiers in cellular neuroscience
N2  - 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.
KW  - adult neurogenesis
KW  - ADP
KW  - ATP
KW  - dentate gyrus
KW  - hippocampus
KW  - microglia
KW  - P2Y13 receptor
KW  - progenitor cell
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47217
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-472174
SN  - 1662-5102
N1  - Copyright © 2018 Stefani, Tschesnokowa, Parrilla, Robaye, Boeynaems, Acker-Palmer, Zimmermann and Gampe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 12
IS  - Art. 134
SP  - 1
EP  - 19
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -