-Amyloid Enhances Glial Glutamate Uptake Activity and
Attenuates Synaptic Efficacy*
Yuji
Ikegaya
§,
Sigeru
Matsuura,
Sayaka
Ueno,
Atsushi
Baba,
Maki K.
Yamada,
Nobuyoshi
Nishiyama, and
Norio
Matsuki
From the Laboratory of Chemical Pharmacology, Graduate School of
Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan
Although amyloid 
-protein (A) has long been
implicated in the pathogenesis of Alzheimer's disease, little is known
about the mechanism by which A causes dementia. A 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 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-induced actin-dependent GLAST redistribution and relevant synaptic malfunction may be a cellular basis for the amnesia of Alzheimer's disease.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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