1. β-Amyloid Enhances Glial Glutamate Uptake Activity and Attenuates Synaptic Efficacy
- Author
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Nobuyoshi Nishiyama, Sayaka Ueno, Norio Matsuki, Maki K. Yamada, Sigeru Matsuura, Atsushi Baba, and Yuji Ikegaya
- Subjects
Programmed cell death ,Patch-Clamp Techniques ,Amino Acid Transport System X-AG ,Glutamic Acid ,Amnesia ,Biology ,Synaptic Transmission ,Biochemistry ,Membrane Potentials ,Pathogenesis ,Glutamatergic ,In vivo ,medicine ,Animals ,Biotinylation ,Molecular Biology ,Cells, Cultured ,Cerebral Cortex ,Aspartic Acid ,Amyloid beta-Peptides ,Glutamate receptor ,Membrane Proteins ,Biological Transport ,Cell Biology ,Peptide Fragments ,In vitro ,Rats ,Cell biology ,Animals, Newborn ,Astrocytes ,Synapses ,medicine.symptom - Abstract
Although amyloid beta-protein (A beta) has long been implicated in the pathogenesis of Alzheimer's disease, little is known about the mechanism by which A beta causes dementia. A beta leads to neuronal cell death in vivo and in vitro, but recent evidence suggests that the property of the amnesic characteristic of Alzheimer's disease can be explained by a malfunction of synapses rather than a loss of neurons. Here we show that prolonged treatment with A beta augments the glutamate clearance ability of cultured astrocytes and induces a dramatic decrease in glutamatergic synaptic activity of neurons cocultured with the astrocytes. Biotinylation assay revealed that the enhancement of glutamate uptake activity was associated with an increase in cell-surface expression of GLAST, a subtype of glial glutamate transporters, without apparent changes in the total amount of GLAST. This phenomenon was blocked efficiently by actin-disrupting agents. Thus, A beta-induced actin-dependent GLAST redistribution and relevant synaptic malfunction may be a cellular basis for the amnesia of Alzheimer's disease.
- Published
- 2002