Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-α
✍ Scribed by Mikael Persson; Mona Brantefjord; Elisabeth Hansson; Lars Rönnbäck
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 403 KB
- Volume
- 51
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
Abstract
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 μM 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‐α (TNF‐α) 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‐α, since this cytokine mimicked the effect of LPS. Furthermore, the effect of LPS was blocked by thalidomide, an inhibitor of TNF‐α synthesis. Additionally, neutralizing antibodies against TNF‐α also blocked the increase, indicating TNF‐α 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. ©2005 Wiley‐Liss, Inc.