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Abstract

ABSTRACT:Alzheimer's disease is a major neurodegenerative disorder in which there is an overproduction and accumulation of amyloid-β (Aβ) peptides. During the initial stages of the disease, glutamate receptors are dysregulated by Aβ accumulation resulting in the disruption of glutamatergic synaptic transmission. We used rat cortical cell cultures to examine the effects of Aβ(25-35)-induced neurotoxicity on glutamine transporters involved in the glutamate cycle. In primary mixed cell cultures prepared from cerebral cortex, incubation with 10 µM Aβ(25-35) for 12 h, but not for 24 h, markedly suppressed system A transporter 1 (SAT1) mRNA expression. On the other hand, Aβ(25-35) had no effect on SAT1 mRNA level in neuronal cell cultures. Treatment of both types of cell cultures with Aβ(25-35) resulted in a significant decrease in cell survival in a concentration and time-dependent manner, as determined by MTT assay. These results indicated that Aβ may impair neuronal function and transmitter synthesis and perhaps reduce excitotoxicity through a reduction in neuronal glutamine uptake.