Microglia express GABA(B) receptors to modulate interleukin release

Susanne A Kuhn; Frank K H van Landeghem; Robert Zacharias; Katrin Färber; Angelika Rappert; Sanja Pavlovic; Anja Hoffmann; Christiane Nolte; Helmut Kettenmann

doi:10.1016/j.mcn.2003.10.023

Microglia express GABA(B) receptors to modulate interleukin release

Mol Cell Neurosci. 2004 Feb;25(2):312-22. doi: 10.1016/j.mcn.2003.10.023.

Authors

Susanne A Kuhn¹, Frank K H van Landeghem, Robert Zacharias, Katrin Färber, Angelika Rappert, Sanja Pavlovic, Anja Hoffmann, Christiane Nolte, Helmut Kettenmann

Affiliation

¹ Department of Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine, D-13125 Berlin, Germany.

PMID: 15019947
DOI: 10.1016/j.mcn.2003.10.023

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Axotomy
Calcium Signaling / drug effects
Calcium Signaling / physiology
Cells, Cultured
Central Nervous System / cytology
Central Nervous System / immunology
Central Nervous System / metabolism*
Facial Nerve Injuries / immunology
Facial Nerve Injuries / pathology
Facial Nerve Injuries / physiopathology
GABA Agonists / pharmacology
GABA-B Receptor Agonists
Gliosis / immunology
Gliosis / metabolism
Gliosis / physiopathology
Interleukin-12 / immunology
Interleukin-12 / metabolism
Interleukin-12 Subunit p40
Interleukin-6 / immunology
Interleukin-6 / metabolism
Interleukins / immunology
Interleukins / metabolism*
Lipopolysaccharides / pharmacology
Mice
Mice, Inbred C57BL
Microglia / drug effects
Microglia / immunology
Microglia / metabolism*
Potassium Channels / drug effects
Potassium Channels / metabolism
Protein Subunits / immunology
Protein Subunits / metabolism
Rats
Rats, Wistar
Receptors, GABA-B / metabolism*
gamma-Aminobutyric Acid / metabolism*

Substances

GABA Agonists
GABA-B Receptor Agonists
Interleukin-12 Subunit p40
Interleukin-6
Interleukins
Lipopolysaccharides
Potassium Channels
Protein Subunits
Receptors, GABA-B
Interleukin-12
gamma-Aminobutyric Acid