Understanding the role of P2X7 in affective disorders - are glial cells the major players?

Stokes, L, Spencer, S and Jenkins, T 2015, 'Understanding the role of P2X7 in affective disorders - are glial cells the major players?', Frontiers in Cellular Neuroscience, vol. 9, 258, pp. 1-6.


Document type: Journal Article
Collection: Journal Articles

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Title Understanding the role of P2X7 in affective disorders - are glial cells the major players?
Author(s) Stokes, L
Spencer, S
Jenkins, T
Year 2015
Journal name Frontiers in Cellular Neuroscience
Volume number 9
Article Number 258
Start page 1
End page 6
Total pages 6
Publisher Frontiers Research Foundation
Abstract Pathophysiology associated with several psychiatric disorders has been linked to inflammatory biomarkers. This has generated a theory of major depressive disorders as an inflammatory disease. The idea of pro-inflammatory cytokines altering behavior is now well accepted however many questions remain. Microglia can produce a plethora of inflammatory cytokines and these cells appear to be critical in the link between inflammatory changes and depressive disorders. Microglia play a known role in sickness behavior which has many components of depressive-like behavior such as social withdrawal, sleep alterations, and anorexia. Numerous candidate genes have been identified for psychiatric disorders in the last decade. Single nucleotide polymorphisms (SNPs) in the human P2X7 gene have been linked to bipolar disorder, depression, and to the severity of depressive symptoms. P2X7 is a ligand-gated cation channel expressed on microglia with lower levels found on astrocytes and on some neuronal populations. In microglia P2X7 is a major regulator of pro-inflammatory cytokines of the interleukin-1 family. Genetic deletion of P2X7 in mice is protective for depressive behavior in addition to inflammatory responses. P2X7-/- mice have been shown to demonstrate anti-depressive-like behavior in forced swim and tail suspension behavioral tests and stressor-induced behavioral responses were blunted. Both neurochemical (norepinephrine, serotonin, and dopamine) and inflammatory changes have been observed in the brains of P2X7-/- mice. This review will discuss the recent evidence for involvement of P2X7 in the pathophysiology of depressive disorders and propose mechanisms by which altered signaling through this ion channel may affect the inflammatory state of the brain.
Subject Animal Physiology - Systems
Keyword(s) P2X7
Depression
Microglia
Inflammation
Mouse Models
SNP
DOI - identifier 10.3389/fncel.2015.00258
Copyright notice © 2015 Stokes, Spencer and Jenkins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor 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.
ISSN 1662-5102
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