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Cited by 509Neuroscience and Neuropharmacology ResearchMultiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration Mechanisms

Inhibitory role for GABA in autoimmune inflammation

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Bhat, Roopa, Axtell, Robert, Mitra, Ananya, Miranda, Melissa, Lock, Christopher, Tsien, Richard W., Steinman, Lawrence·2010·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0915139107PMC PMC2823917
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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.

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  • Activation of GABA receptors leads to Ca2+-influx stimulating or activation of PI3K/Akt/PKB pathway resulting in increased insulin release, promotes pancreatic β-cell proliferation, and inhibits apoptosis.

    “Pancreas β-cells express gamma amino butyric acid receptor A/B (GABAA/BRs) and activation of GABA receptors leads to Ca2+-influx stimulating or activation of PI3K/Akt/PKB pathway resulting in increased insulin release promotes pancreatic β-cells proliferation and inhibits apoptosis.”

    From A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. (2024) · cites this paper as [104]

    The Results describe GABA-A receptor signaling in macrophages and other antigen-presenting cells, including changes in MAPK phosphorylation and inflammatory cytokine production. Searches for pancreatic β-cells, insulin release, Ca2+ influx, PI3K/Akt/PKB, proliferation, and apoptosis found no passage addressing the attributed β-cell effects. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • GABA regulates both the survival and regeneration of human pancreatic β-cells.

    “Thus, GABA regulates both the survival and regeneration of human pancreatic β-cells.”

    From A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. (2024) · cites this paper as [104]

    The Abstract and Results describe GABA’s effects on immune cells and autoimmune inflammation, including a mouse model of multiple sclerosis. Searches for human pancreatic β-cells, their survival, and their regeneration found no passage addressing those outcomes. Page numbers were unavailable in our copy. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Bhat, R., Axtell, R., Mitra, A., Miranda, M., Lock, C., Tsien, R. W., & Steinman, L.
Affiliations
  • Stanford Medicine (US)
  • Department of Neurology and Neurological Sciences and
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2010-02
Volume
107
Issue
6
Pages
2580-2585
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0915139107
PMC
PMC2823917
OpenAlex
W1993918716
Cited by
509
References
1
Citations by year
2026: 32 · 2025: 39 · 2024: 36 · 2023: 34 · 2022: 41 · 2021: 47 · 2020: 31 · 2019: 27 · 2018: 23 · 2017: 33 · 2016: 32 · 2015: 24 · 2014: 26 · 2013: 23 · 2012: 24
FWCI
10.87
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Multiple Sclerosis Society
  • National Institute of Neurological Disorders and Stroke (NS 24067, R01NS024067)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
GABA, antigen-presenting cells, GABA receptors, experimental autoimmune encephalomyelitis, multiple sclerosis, neuroinflammation, MAPK signaling, myelin antigens, immunomodulation, paralysis
MeSH terms
4-Aminobutyrate Transaminase, Animals, Antigen-Presenting Cells, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental, gamma-Aminobutyric Acid, Inflammation, Interferon-gamma, Macrophages, Membrane Potentials, Mice, Inbred C57BL, Mice, Transgenic, Multiple Sclerosis, Myelin Proteins, T-Lymphocytes, Blotting, Western, Receptors, GABA, Patch-Clamp Techniques, GABA Agents, Myelin-Associated Glycoprotein, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-17, GABA Plasma Membrane Transport Proteins, Mice, Myelin-Oligodendrocyte Glycoprotein

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