Microglia express GABA(B) receptors to modulate interleukin release
Abstract
gamma-Aminobutyric acid (GABA) can act as a neuroprotective agent besides its well-established role as the main inhibitory neurotransmitter in the CNS. Here we report that microglial cells express GABA(B) receptors indicating that these prominent immunocompetent cells in the brain are a target for GABA. Agonists of GABA(B) receptors triggered the induction of K(+) conductance in microglial cells from acute brain slices and in culture. Both subunits of GABA(B) receptors were identified in cultured microglia by Western blot analysis and immunocytochemistry, and were detected on a subpopulation of microglia in situ by immunohistochemistry. In response to facial nerve axotomy, we observed an increase in GABA(B) receptor expressing microglial cells in the facial nucleus. We activated microglial cells in culture with lipopolysaccharide (LPS) to induce the release of interleukin-6 and interleukin-12p40. This release activity was attenuated by simultaneous activation of the GABA(B) receptors indicating that GABA can modulate the microglial immune response.
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High expression of GABA receptor (Gabra6) may play a role in inhibiting microglial cytokine release and attenuating microglial activation.
“In addition, the high expression of GABA receptor (Gabra6, second most enriched DEG in cluster3 microglia) may also play a role in inhibiting microglial cytokine release (Kuhn et al., 2004) and attenuating microglial activation.”
From Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms (2021) · cites this paper as Kuhn et al., 2004
Cites
Boucsein, C., Zacharias, R., Färber, K., Pavlovic, S., Hanisch, U., & Kettenmann, H. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02663.x · Cited by 203 · see citing works
Self-citationElectrophysiological properties of microglial cells in normal and pathologic rat brain slices
Boucsein, C., Kettenmann, H., & Nolte, C. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00100.x · Cited by 166 · see citing works
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Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Neurotransmitter receptors on microglia
Pocock, J. M., & Kettenmann, H. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.07.007 · Cited by 650 · see citing works
Self-citationOwen, D. R., Narayan, N., Wells, L., Healy, L., Smyth, E., Rabiner, E. A., Galloway, D., Williams, J. B., Lehr, J., Mandhair, H., et al. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17710182 · Cited by 194 · see citing works
“Microglia also express receptors for neurotransmitters including g-aminobutyric acid (GABA) and glutamate, providing another pathway for microglial phenotypic regulation.(1,50,51) Caution should therefore be used when extrapolating these findings in vivo and further work will therefore examine directly how TSPO expres…”
BackgroundCrowley, T., Cryan, J. F., Downer, E. J., & O’Leary, O. F. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.02.001 · Cited by 150 · see citing works
Shi, Y., Andhey, P. S., Ising, C., Wang, K., Snipes, L. L., Boyer, K., Lawson, S., Yamada, K., Qin, W., Manis, M., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.05.034 · Cited by 135 · see citing works
Microglial modulation of neuronal activity in the healthy brain
York, E. M., Bernier, L., & MacVicar, B. A. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22571 · Cited by 98 · see citing works
Regulation of the neurodegenerative process associated to Parkinson's disease by CD4+ T-cells
González, H., Contreras, F., & Pacheco, R. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9618-9 · Cited by 70 · see citing works
- Authors
- Kuhn, S. A., van Landeghem, F. K. H., Zacharias, R., Färber, K., Rappert, A., Pavlovic, S., Hoffmann, A., Nolte, C., & Kettenmann, H.
- Affiliations
- Max Delbrück Center (DE)
- Corresponding author
- Kettenmann, Helmut
- ORCID
- Kettenmann, Helmut
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 25
- Issue
- 2
- Pages
- 312-322
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W2096877847
- Cited by
- 218
- References
- 2
- Citations by year
- 2026: 13 · 2025: 7 · 2024: 10 · 2023: 19 · 2022: 13 · 2021: 19 · 2020: 14 · 2019: 16 · 2018: 8 · 2017: 9 · 2016: 15 · 2015: 10 · 2014: 17 · 2013: 3 · 2012: 7
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- GABAB receptors, microglia, GABA, interleukin-6, interleukin-12p40, microglial activation, lipopolysaccharide, facial nerve axotomy, facial nucleus, potassium conductance, neuroinflammation, neuroprotection
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Central Nervous System, gamma-Aminobutyric Acid, Gliosis, Interleukins, Lipopolysaccharides, Mice, Inbred C57BL, Potassium Channels, Interleukin-6, Rats, Wistar, Microglia, Receptors, GABA-B, Interleukin-12, GABA Agonists, Axotomy, Calcium Signaling, Facial Nerve Injuries, Protein Subunits, Mice, Rats, Interleukin-12 Subunit p40, GABA-B Receptor Agonists
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