P2X7 Receptors Regulate Phagocytosis and Proliferation in Adult Hippocampal and SVZ Neural Progenitor Cells: Implications for Inflammation in Neurogenesis

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Identifying the signalling mechanisms that regulate adult neurogenesis is essential to understanding how the brain may respond to neuro‐inflammatory events. P2X7 receptors can regulate pro‐inflammatory responses, and in addition to their role as cation channels they can trigger cell death and mediate phagocytosis. How P2X7 receptors may regulate adult neurogenesis is currently unclear. Here, neural progenitor cells (NPCs) derived from adult murine hippocampal subgranular (SGZ) and cerebral subventricular (SVZ) zones were utilized to characterise the roles of P2X7 in adult neurogenesis, and assess the effects of high extracellular ATP, characteristic of inflammation, on NPCs. Immunocytochemistry found NPCs in vivo and in vitro expressed P2X7, and the activity of P2X7 in culture was demonstrated using calcium influx and pore formation assays. Live cell and confocal microscopy, in conjunction with flow cytometry, revealed P2X7+ NPCs were able to phagocytose fluorescent beads, and this was inhibited by ATP, indicative of P2X7 involvement. Further, P2X7 receptors were activated with ATP or BzATP, and 5‐ethynyl‐2'‐deoxyuridine (EdU) used to observe a dose‐dependent decrease in NPC proliferation. A role for P2X7 in decreased NPC proliferation was confirmed using chemical inhibition and NPCs from P2X7–/– mice. Together, these data present three distinct roles for P2X7 during adult neurogenesis, depending on extracellular ATP concentrations: (i) P2X7 receptors can form transmembrane pores leading to cell death, (ii) P2X7 receptors can regulate rates of proliferation, likely via calcium signalling and (iii) P2X7 can function as scavenger receptors in the absence of ATP, allowing NPCs to phagocytose apoptotic NPCs during neurogenesis. © AlphaMed Press 2018
Funding Information
  • Alma Hazel Eddy Trust
  • Australian Research Council (FT120100581)
  • Baxter Charitable Foundation
  • Brian M. Kirby Foundation
  • International Retinal Research Foundation (Charles D. Kelman, M.D. Postdoctoral Award (2010))
  • National Health and Medical Research Council (104808210614191120095571100)
  • Victorian Government Operational Infrastructure Support Grant
  • International Retinal Research Foundation
  • Victorian Government
  • ARC
  • National Health and Medical Research Council (NHMRC) of Australia
  • Rebecca L. Cooper Medical Research Foundation
  • Australian Research Council (FT120100581)
  • International Retinal Research Foundation (Charles D. Kelman, M.D. Postdoctoral Award (2010))
  • National Health and Medical Research Council (104808210614191120095571100)
  • University of South Alabama
  • State Government of Victoria
  • ARC
  • National Health and Medical Research Council
  • Rebecca L. Cooper Medical Research Foundation

This publication has 69 references indexed in Scilit: