Amyloid β protein enhances the clearance of extracellular L-glutamate by cultured rat cortical astrocytes

To explore the impact of Alzheimer's disease amyloid beta protein (Abeta) on astrocyte functions, we investigated the effect of Abeta on glutamate clearance capacity of cultured rat cortical astrocytes. When L-glutamate (50-200 muM) was added to astrocyte cultures and incubated, the extracellular L-glutamate concentration declined with time. The time-dependent decline of extracellular L-glutamate was significantly faster in cultures treated with 10-20 M Abeta for 24 h than in intact cultures, suggesting that Abeta enhances the L-glutamate clearance capacity of astrocytes. The effect of Abeta was not affected by antioxidants including catalase, propyl gallate or Trolox. Relatively long treatment time (8-48 h) was required for Abeta to exert this effect. Western blot analysis revealed that expression level of the glutamate transporter GLAST was increased by treatment with 10-20 muM Abeta for 8-48 It. These results suggest that Abeta upregulates a glutamate uptake system of astrocytes and enhances the clearance of extracellular L-glutamate. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.