title: Amyloid beta protein enhances the clearance of extracellular L-glutamate by cultured rat cortical astrocytes.
abstract: 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 microM) 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 microM 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 microM Abeta for 8-48 h. These results suggest that Abeta upregulates a glutamate uptake system of astrocytes and enhances the clearance of extracellular L-glutamate.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo 142-8501, Japan. abe@hoshi.ac.jp
authors.forename: Kazuho
authors.initials: K
authors.lastname: Abe
authors.forename: Miwa
authors.initials: M
authors.lastname: Misawa
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D027322:Amino Acid Transport System X-AG; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018698:Glutamic Acid