title: Inhibiting neuroinflammation: The role and therapeutic potential of GABA in neuro-immune interactions.
abstract: The central nervous system, once thought to be a site of immunological privilege, has since been found to harbour immunocompetent cells and to communicate with the peripheral nervous system. In the central nervous system (CNS), glial cells display immunological responses to pathological and physiological stimuli through pro- and anti-inflammatory cytokine and chemokine signalling, antigen presentation and the clearing of cellular debris through phagocytosis. While this neuroinflammatory signalling can act to reduce neuronal damage and comprises a key facet of CNS homeostasis, persistent inflammation or auto-antigen-mediated immunoreactivity can induce a positive feedback cycle of neuroinflammation that ultimately results in necrosis of glia and neurons. Persistent neuroinflammation has been recognised as a major pathological component of virtually all neurodegenerative diseases and has also been a focus of research into the pathology underlying psychiatric disorders. Thus, pharmacological strategies to curb the pathological effects of persistent neuroinflammation are of interest for many disorders of the CNS. Accumulating evidence suggests that GABAergic activities are closely bound to immune processes and signals, and thus the GABAergic neurotransmitter system might represent an important therapeutic target in modulating neuroinflammation. Here, we review evidence that inflammation induces changes in the GABA neurotransmitter system in the CNS and that GABAergic signalling exerts a reciprocal influence over neuroinflammatory processes. Together, the data support the hypothesis that the GABA system is a potential therapeutic target in the modulation of central inflammation.
authors: Department of Anatomy and Neuroscience, University College Cork, Ireland.
authors: Tadhg
authors: T
authors: Crowley
authors: Department of Anatomy and Neuroscience, University College Cork, Ireland; APC Microbiome Institute, University College Cork, Ireland.
authors: John F
authors: JF
authors: Cryan
authors: School of Medicine, Discipline of Physiology, Trinity Biomedical Sciences Institute, Trinity College, Dublin 2, Ireland. Electronic address: edowner@tcd.ie.
authors: Eric J
authors: EJ
authors: Downer
authors: Department of Anatomy and Neuroscience, University College Cork, Ireland; APC Microbiome Institute, University College Cork, Ireland. Electronic address: o.oleary@ucc.ie.
authors: Olivia F
authors: OF
authors: O'Leary
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018755:GABA Agonists / Q000378:metabolism; D018756:GABA Antagonists / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015213:Neuroimmunomodulation / Q000276:immunology*; D018079:Receptors, GABA / Q000276:immunology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid
keywords: Baclofen; GABA; GABA(A) receptor; GABA(B) receptor; Glia; Inflammation; Neuroinflammation; Toll-like receptor