Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

PNAS 107 (6): 2580-2585

Copyright © 2010 by the National Academy of Sciences.


Inhibitory role for GABA in autoimmune inflammation

Roopa Bhat a , 1 , Robert Axtell a , Ananya Mitra b , Melissa Miranda a , Christopher Lock a , Richard W. Tsien b , and Lawrence Steinman a

aDepartment of Neurology and Neurological Sciences and bDepartment of Molecular and Cellular Physiology, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305

Contributed by Richard W. Tsien, December 31, 2009 (sent for review November 30, 2009)

Abstract: GABA, the principal inhibitory neurotransmitter in the adult brain, has a parallel inhibitory role in the immune system. We demonstrate that immune cells synthesize GABA and have the machinery for GABA catabolism. Antigen-presenting cells (APCs) express functional GABA receptors and respond electrophysiologically to GABA. Thus, the immune system harbors all of the necessary constituents for GABA signaling, and GABA itself may function as a paracrine or autocrine factor. These observations led us to ask further whether manipulation of the GABA pathway influences an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Increasing GABAergic activity ameliorates ongoing paralysis in EAE via inhibition of inflammation. GABAergic agents act directly on APCs, decreasing MAPK signals and diminishing subsequent adaptive inflammatory responses to myelin proteins.

Key Words: experimental autoimmune encephalomyelitis • multiple sclerosis • neurotransmitter • antigen-presenting cells

Author contributions: R.B., R.A., A.M., C.L., and L.S. designed research; R.B., R.A., A.M., and M.M. performed research; R.B., R.A., A.M., and M.M. analyzed data; and R.B., R.A., A.M., C.L., R.W.T., and L.S. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at

1To whom correspondence may be addressed. E-mail: roopa.bhat{at} or rwtsien{at}

GABAergic System in {beta}-Cells: From Autoimmunity Target to Regeneration Tool.
P. Fiorina (2013)
Diabetes 62, 3674-3676
   Full Text »    PDF »
{gamma}-Aminobutyric Acid Regulates Both the Survival and Replication of Human {beta}-Cells.
J. Tian, H. Dang, Z. Chen, A. Guan, Y. Jin, M. A. Atkinson, and D. L. Kaufman (2013)
Diabetes 62, 3760-3765
   Abstract »    Full Text »    PDF »
Pepper Arginine Decarboxylase Is Required for Polyamine and {gamma}-Aminobutyric Acid Signaling in Cell Death and Defense Response.
N. H. Kim, B. S. Kim, and B. K. Hwang (2013)
Plant Physiology 162, 2067-2083
   Abstract »    Full Text »    PDF »
Systemic Lack of Canonical Histamine Receptor Signaling Results in Increased Resistance to Autoimmune Encephalomyelitis.
N. Saligrama, L. K. Case, R. del Rio, R. Noubade, and C. Teuscher (2013)
J. Immunol. 191, 614-622
   Abstract »    Full Text »    PDF »
Propofol Inhibits Superoxide Production, Elastase Release, and Chemotaxis in Formyl Peptide-Activated Human Neutrophils by Blocking Formyl Peptide Receptor 1.
S.-C. Yang, P.-J. Chung, C.-M. Ho, C.-Y. Kuo, M.-F. Hung, Y.-T. Huang, W.-Y. Chang, Y.-W. Chang, K.-H. Chan, and T.-L. Hwang (2013)
J. Immunol. 190, 6511-6519
   Abstract »    Full Text »    PDF »
The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population-based cohort.
E. Obiora, R. Hubbard, R. D. Sanders, and P. R. Myles (2013)
Thorax 68, 163-170
   Abstract »    Full Text »    PDF »
Piet Mondrian's trees and the evolution in understanding multiple sclerosis, Charcot Prize Lecture 2011.
L. Steinman, R. C. Axtell, D. Barbieri, R. Bhat, S. E. Brownell, B. A. de Jong, S. E. Dunn, J. L. Grant, M. H. Han, P. P. Ho, et al. (2013)
Multiple Sclerosis Journal 19, 5-14
   Abstract »    Full Text »    PDF »
Inflammation inhibits GABA transmission in multiple sclerosis.
S. Rossi, V. Studer, C. Motta, V. De Chiara, F. Barbieri, G. Bernardi, and D. Centonze (2012)
Multiple Sclerosis Journal 18, 1633-1635
   Abstract »    Full Text »    PDF »
Neuroactive steroids, their metabolites, and neuroinflammation.
S. Giatti, M. Boraso, R. C. Melcangi, and B. Viviani (2012)
J. Mol. Endocrinol. 49, R125-R134
   Abstract »    Full Text »    PDF »
Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice.
M. H. Han, D. H. Lundgren, S. Jaiswal, M. Chao, K. L. Graham, C. S. Garris, R. C. Axtell, P. P. Ho, C. B. Lock, J. I. Woodard, et al. (2012)
J. Exp. Med. 209, 1325-1334
   Abstract »    Full Text »    PDF »
Stimulation of Dopamine Receptor D5 Expressed on Dendritic Cells Potentiates Th17-Mediated Immunity.
C. Prado, F. Contreras, H. Gonzalez, P. Diaz, D. Elgueta, M. Barrientos, A. A. Herrada, A. Lladser, S. Bernales, and R. Pacheco (2012)
J. Immunol. 188, 3062-3070
   Abstract »    Full Text »    PDF »
Potential role of IL-13 in neuroprotection and cortical excitability regulation in multiple sclerosis.
S. Rossi, R. Mancino, A. Bergami, F. Mori, M. Castelli, V. De Chiara, V. Studer, G. Mataluni, G. Sancesario, V. Parisi, et al. (2011)
Multiple Sclerosis Journal 17, 1301-1312
   Abstract »    Full Text »    PDF »
Impaired neurosteroid synthesis in multiple sclerosis.
F. Noorbakhsh, K. K. Ellestad, F. Maingat, K. G. Warren, M. H. Han, L. Steinman, G. B. Baker, and C. Power (2011)
Brain 134, 2703-2721
   Abstract »    Full Text »    PDF »
Computational Repositioning of the Anticonvulsant Topiramate for Inflammatory Bowel Disease.
J. T. Dudley, M. Sirota, M. Shenoy, R. K. Pai, S. Roedder, A. P. Chiang, A. A. Morgan, M. M. Sarwal, P. J. Pasricha, and A. J. Butte (2011)
Science Translational Medicine 3, 96ra76
   Abstract »    Full Text »    PDF »
Systemic augmentation of {alpha}B-crystallin provides therapeutic benefit twelve hours post-stroke onset via immune modulation.
A. Arac, S. E. Brownell, J. B. Rothbard, C. Chen, R. M. Ko, M. P. Pereira, G. W. Albers, L. Steinman, and G. K. Steinberg (2011)
PNAS 108, 13287-13292
   Abstract »    Full Text »    PDF »
GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes.
N. Soltani, H. Qiu, M. Aleksic, Y. Glinka, F. Zhao, R. Liu, Y. Li, N. Zhang, R. Chakrabarti, T. Ng, et al. (2011)
PNAS 108, 11692-11697
   Abstract »    Full Text »    PDF »
Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging.
O. Albayram, J. Alferink, J. Pitsch, A. Piyanova, K. Neitzert, K. Poppensieker, D. Mauer, K. Michel, A. Legler, A. Becker, et al. (2011)
PNAS 108, 11256-11261
   Abstract »    Full Text »    PDF »
Critical appraisal of animal models of multiple sclerosis.
D. Baker, W. Gerritsen, J. Rundle, and S. Amor (2011)
Multiple Sclerosis Journal 17, 647-657
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882