Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/15087
Title: Systemic treatment with the inhibitory neurotransmitter gamma-aminobutyric acid aggravates experimental autoimmune encephalomyelitis by affecting proinflammatory immune responses
Authors: CARMANS, Sofie 
HENDRIKS, Jerome 
Slaets, Helena
THEWISSEN, Kristof 
STINISSEN, Piet 
RIGO, Jean-Michel 
HELLINGS, Niels 
Issue Date: 2013
Publisher: ELSEVIER SCIENCE BV
Source: JOURNAL OF NEUROIMMUNOLOGY, 255 (1-2), p. 45-53
Abstract: Transcriptomic and proteomic analyses of multiple sclerosis (MS) lesions indicate alterations in the gamma-aminobutyric acid (GABA) inhibitory system, suggesting its involvement in the disease process. To further elucidate the role of GABA in central nervous system (CNS) inflammation in vivo, the chronic myelin oligodendrocyte glycoprotein (MOG)(35-55) experimental autoimmune encephalomyelitis (EAE) model was used. Daily GABA injections (200 mg/kg) from day 3 onwards significantly augmented disease severity, which was associated with increased CNS mRNA expression levels of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6. GABA-treated mice showed enhanced MUG-dependent proliferation and were skewed towards a T helper 1 phenotype. Moreover, in vitro, the lipopolysaccharide (LPS)-induced increase in interleukin (IL)-6 production by macrophages was enhanced at low GABA concentrations (0.03-0.3 mM). In sharp contrast to exogenous GABA administration, endogenous GABA increment by systemic treatment with the GABA-transaminase inhibitor vigabatrin (250 mg/kg) had prophylactic as well as therapeutic potential in EAE. Together, these results indicate an immune amplifying role of GABA in neuroinflammatory diseases like MS.
Notes: [Carmans, Sofie; Hendriks, Jerome J. A.; Slaets, Helena; Thewissen, Kristof; Stinissen, Piet; Rigo, Jean-Michel; Hellings, Niels] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium.
Keywords: Immunology; Neurosciences; multiple sclerosis; experimental autoimmune encephalomyelitis; gammo-amino butyric acid; vigabatrin; macrophage; T cell;Multiple sclerosis; Experimental autoimmune encephalomyelitis; Gamma amino-butyric acid; Vigabatrin, macrophage, T cell
Document URI: http://hdl.handle.net/1942/15087
ISSN: 0165-5728
e-ISSN: 1872-8421
DOI: 10.1016/j.jneuroim.2012.11.001
ISI #: 000315014700006
Category: A1
Type: Journal Contribution
Validations: ecoom 2014
Appears in Collections:Research publications

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