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ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics

Wei L 1 , Syed Mortadza SA 2 , Yan J 3 , Zhang L 3 , Wang L 3 , Yin Y 3 Show all authors , Li C 3 , Chalon S 4 , Emond P 5 , Belzung C 4 , Li D 6 , Lu C 6 , Roger S 7 , Jiang LH 8

Affiliations 

  • 1 Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, Xinxiang Medical University, China; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, United Kingdom
  • 2 School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, United Kingdom; Faculty of Medicine and Health Science, University Putra Malaysia, Selangor, Malaysia
  • 3 Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, Xinxiang Medical University, China
  • 4 Inserm UMR 1253, iBrain, Université de Tours, Tours, France
  • 5 Inserm UMR 1253, iBrain, Université de Tours, Tours, France; CHRU de Tours, Service de Médecine Nucléaire In Vitro, Tours, France
  • 6 Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, Xinxiang Medical University, China; Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical University, China
  • 7 Inserm UMR1069, Nutrition, Croissance et Cancer, Université de Tours, France; Institut Universitaire de France, Paris Cedex 05, France
  • 8 Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, Xinxiang Medical University, China; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, United Kingdom; Institut Universitaire de France, Paris Cedex 05, France. Electronic address: l.h.jiang@leeds.ac.uk
Neurosci Biobehav Rev, 2018 Apr;87:192-205.
PMID: 29453990 DOI: 10.1016/j.neubiorev.2018.02.005

Abstract

Mood disorders are a group of psychiatric conditions that represent leading global disease burdens. Increasing evidence from clinical and preclinical studies supports that innate immune system dysfunction plays an important part in the pathophysiology of mood disorders. P2X7 receptor, belonging to the ligand-gated ion channel P2X subfamily of purinergic P2 receptors for extracellular ATP, is highly expressed in immune cells including microglia in the central nervous system (CNS) and has a vital role in mediating innate immune response. The P2X7 receptor is also important in neuron-glia signalling in the CNS. The gene encoding human P2X7 receptor is located in a locus of susceptibility to mood disorders. In this review, we will discuss the recent progress in understanding the role of the P2X7 receptor in the pathogenesis and development of mood disorders and in discovering CNS-penetrable P2X7 antagonists for potential uses in in vivo imaging to monitor brain inflammation and antidepressant therapeutics.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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