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P2X7 receptor signaling during adult hippocampal neurogenesis

摘要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 con-solidation 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 re-ceptors 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 exceptional-ly 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.

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作者单位 Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia;Grifth Institute for Drug Discovery, Grifth University, Brisbane, Queensland, Australia [1] Discipline of Anatomy and Histology, School of Medical Science, The University of Sydney, Sydney, New South Wales, Australia;Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia [2] Discipline of Anatomy and Histology, School of Medical Science, The University of Sydney, Sydney, New South Wales, Australia;Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St. Vincent’s Centre for Applied Medical Research, Sydney, New South Wales, Australia;Faculty of Medicine, St. Vincent’s Clinical School, University of New South Wales Sydney, Sydney, New South Wales, Australia [3] School of Environment and Science, Grifth University, Brisbane, Queensland, Australia [4] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia [5] Grifth Institute for Drug Discovery, Grifth University, Brisbane, Queensland, Australia;Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia;School of Environment and Science, Grifth University, Brisbane, Queensland, Australia [6]
栏目名称 REVIEW
DOI 10.4103/1673-5374.257510
发布时间 2019-07-25
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中国神经再生研究(英文版)

中国神经再生研究(英文版)

2019年14卷10期

1684-1694页

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