Microglia express GABAB receptors to modulate interleukin release

被引:162
作者
Kuhn, SA
van Landeghem, FKH
Zacharias, R
Färber, K
Rappert, A
Pavlovic, S
Hoffmann, A
Nolte, C
Kettenmann, H
机构
[1] Max Delbruck Ctr Mol Med, Dept Cellular Neurosci, D-13125 Berlin, Germany
[2] Humboldt Univ, Charite, Inst Neuropathol, D-13353 Berlin, Germany
关键词
D O I
10.1016/j.mcn.2003.10.023
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 interieukin-12p40. This release activity was attenuated by simultaneous activation of the GABA(B) receptors indicating that GABA can modulate the microglial immune response. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:312 / 322
页数:11
相关论文
共 30 条
[1]   DISPLACEMENT OF SYNAPTIC TERMINALS FROM REGENERATING MOTONEURONS BY MICROGLIAL CELLS [J].
BLINZING.K ;
KREUTZBE.G .
ZEITSCHRIFT FUR ZELLFORSCHUNG UND MIKROSKOPISCHE ANATOMIE, 1968, 85 (02) :145-&
[2]   Electrophysiological actions of GABA(B) agonists and antagonists in rat dorso-lateral septal neurones in vitro [J].
Bon, C ;
Galvan, M .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 118 (04) :961-967
[3]   Purinergic receptors on microglial cells:: functional expression in acute brain slices and modulation of microglial activation in vitro [J].
Boucsein, C ;
Zacharias, R ;
Färber, K ;
Pavlovic, S ;
Hanisch, UK ;
Kettenmann, H .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2003, 17 (11) :2267-2276
[4]   Electrophysiological properties of microglial cells in normal and pathologic rat brain slices [J].
Boucsein, C ;
Kettenmann, H ;
Nolte, C .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (06) :2049-2058
[5]  
CHOI DW, 1990, ANNU REV NEUROSCI, V13, P171, DOI 10.1146/annurev.neuro.13.1.171
[6]  
FERN R, 1995, J NEUROSCI, V15, P699
[7]   GABAB-receptor splice variants GB1a and GB1b in rat brain:: developmental regulation, cellular distribution and extrasynaptic localization [J].
Fritschy, JM ;
Meskenaite, V ;
Weinmann, O ;
Honer, M ;
Benke, D ;
Mohler, H .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1999, 11 (03) :761-768
[8]  
GIULIAN D, 1986, J NEUROSCI, V6, P2163
[9]   ANALYSIS OF NITRATE, NITRITE, AND [N-15]-LABELED NITRATE IN BIOLOGICAL-FLUIDS [J].
GREEN, LC ;
WAGNER, DA ;
GLOGOWSKI, J ;
SKIPPER, PL ;
WISHNOK, JS ;
TANNENBAUM, SR .
ANALYTICAL BIOCHEMISTRY, 1982, 126 (01) :131-138
[10]   ATP-induced membrane currents in ameboid microglia acutely isolated from mouse brain slices [J].
Haas, S ;
Brockhaus, J ;
Verkhratsky, A ;
Kettenmann, H .
NEUROSCIENCE, 1996, 75 (01) :257-261