Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (10): 1684-1694.doi: 10.4103/1673-5374.257510

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P2X7 receptor signaling during adult hippocampal neurogenesis

Hannah C. Leeson 1, 2, Tailoi Chan-Ling 3, 4, Michael D. Lovelace 3, 5, 6, Jeremy C. Brownlie 7, Ben J. Gu 8, Michael W. Weible II 2, 4, 7   

  1. 1 Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia
    2 Griffith Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia
    3 Discipline of Anatomy and Histology, School of Medical Science, The University of Sydney, Sydney, New South Wales, Australia
    4 Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia
    5 Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St. Vincent’s Centre for Applied Medical Research, Sydney, New South Wales, Australia
    6 Faculty of Medicine, St. Vincent’s Clinical School, University of New South Wales Sydney, Sydney, New South Wales, Australia
    7 School of Environment and Science, Griffith University, Brisbane, Queensland, Australia
    8 Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia
  • Online:2019-10-15 Published:2019-10-15
  • Contact: Michael W. Weible II, PhD, m.weible@griffith.edu.au; Ben J. Gu, PhD, ben.gu@florey.edu.au.

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Abstract:

Neurogenesis is a persistent and essential feature of the adult mammalian hippocampus. Granular neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation of new memories. Regulation of hippocampal neurogenesis is complex and multifaceted, and numerous signaling pathways converge to modulate cell proliferation, apoptosis, and clearance of cellular debris, as well as synaptic integration of newborn immature neurons. The expression of functional P2X7 receptors in the central nervous system has attracted much interest and the regulatory role of this purinergic receptor during adult neurogenesis has only recently begun to be explored. P2X7 receptors are exceptionally versatile: in their canonical role they act as adenosine triphosphate-gated calcium channels and facilitate calcium-signaling cascades exerting control over the cell via calcium-encoded sensory proteins and transcription factor activation. P2X7 also mediates transmembrane pore formation to regulate cytokine release and facilitate extracellular communication, and when persistently stimulated by high extracellular adenosine triphosphate levels large P2X7 pores form, which induce apoptotic cell death through cytosolic ion dysregulation. Lastly, as a scavenger receptor P2X7 directly facilitates phagocytosis of the cellular debris that arises during neurogenesis, as well as during some disease states. Understanding how P2X7 receptors regulate the physiology of stem and progenitor cells in the adult hippocampus is an important step towards developing useful therapeutic models for regenerative medicine. This review considers the relevant aspects of adult hippocampal neurogenesis and explores how P2X7 receptor activity may influence the molecular physiology of the hippocampus, and neural stem and progenitor cells.

Key words: P2X7, P2X7R, adult neurogenesis, neural stem cells, neural progenitor cells, hippocampus, SGZ, calcium signaling, purinergic signaling