Disruption of the microglial ADP receptor P2Y13 enhances adult hippocampal neurogenesis

  • 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.

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Author:Jennifer Stefani, Olga Tschesnokowa, Marta Parrilla, Bernard Robaye, Jean-Marie Boeynaems, Amparo Acker-PalmerORCiDGND, Herbert Zimmermann, Kristine Gampe
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29867367
Parent Title (English):Frontiers in cellular neuroscience
Publisher:Frontiers Research Foundation
Place of publication:Lausanne
Contributor(s):Oscar Gonzalez-Perez
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/05/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/08/16
Tag:ADP; ATP; P2Y13 receptor; adult neurogenesis; dentate gyrus; hippocampus; microglia; progenitor cell
Issue:Art. 134
Page Number:19
First Page:1
Last Page:19
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.
Institutes:Biowissenschaften / Biowissenschaften
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
Wissenschaftliche Zentren und koordinierte Programme / Interdisziplinäres Zentrum für Neurowissenschaften Frankfurt (IZNF)
Angeschlossene und kooperierende Institutionen / MPI für Hirnforschung
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 4.0