L-glutamate suppresses amyloid beta-protein-induced stellation of cultured rat cortical astrocytes.
Alzheimer's amyloid beta-protein (Abeta) has been reported to potentiate glutamate toxicity in neurons, but very little is known about interaction between Abeta and glutamate in astrocytes. Therefore, in the present study, we investigated the effects of Abeta and glutamate on morphology of astrocytes. Cultured rat cortical astrocytes exhibited polygonal morphology in the absence of stimulation and differentiated into process-bearing stellate cells following exposure to Abeta (20 microM). L-Glutamate (30-1,000 microM) had no effect on astrocyte morphology in the absence of stimulation but strongly suppressed Abeta-induced stellation. The suppressive effect of L-glutamate on Abeta-induced stellation was not mimicked by glutamate receptor agonists and not blocked by glutamate receptor antagonists. In contrast, the suppressive effect of L-glutamate was mimicked by D- and L-aspartate and transportable glutamate uptake inhibitors. These results suggest that Abeta-induced astrocyte stellation is suppressed by a mechanism related to glutamate transporters.
Abe
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan. kazuhoab@mol.f.u-tokyo.ac.jp
Saito
H
H
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology
D016229:Amyloid beta-Peptides; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018698:Glutamic Acid