Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-alpha.
This study investigates the effect of microglial activation on microglial glutamate transporters in vitro. Stimuli known to activate microglia and/or to be associated with pathological conditions with an impaired astroglial glutamate uptake were compared. Morphological changes and marked increases in ED1 antigen expression were found after 8-h incubation of rat microglia in 56 mM KCl, 1 ng/ml lipopolysaccharide (LPS), and 100 microM glutamate, as well as in acidic and basic conditions, showing that the cells were activated. Of the stimuli used, only LPS induced a significant release of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and was the only stimulus that increased microglial GLT-1 expression and glutamate uptake capacity after 12-h incubation. This effect was probably mediated by TNF-alpha, since this cytokine mimicked the effect of LPS. Furthermore, the effect of LPS was blocked by thalidomide, an inhibitor of TNF-alpha synthesis. Additionally, neutralizing antibodies against TNF-alpha also blocked the increase, indicating TNF-alpha as an inducer of GLT-1 expression in microglia. It was also found that preincubation with glutamate dose-dependently inhibited the microglial glutamate uptake. This could suggest different physiological functions for microglial and astroglial glutamate uptake and might indicate a reciprocal control of GLT-1 expression between microglia and astrocytes.
Persson
Mikael
M
Institute of Clinical Neuroscience, Göteborg University, Göteborg, Sweden. mikael.persson@neuro.gu.se
Brantefjord
Mona
M
Hansson
Elisabeth
E
Rönnbäck
Lars
L
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D053331:Ectodysplasins; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D053331:Ectodysplasins; D027342:Excitatory Amino Acid Transporter 2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D011189:Potassium Chloride