The inhibitory effects of beta-amyloid on glutamate and glucose uptakes by cultured astrocytes

beta-Amyloid is the primary protein component of neuritic plaques, which are degenerative foci in brains of patients with Alzheimer's disease (AD). The effects of this naturally occurring beta-amyloid on the cells of the central nervous system have not been completely understood. beta-Amyloid increases the vulnerability of cultured neurons to glutamate-induced excitotoxic damage. Because astrocytes play a key role in uptake of extracellular glutamate and glutamate uptake is ATP-dependent, we studied the effect of beta 25-35 on glutamate and glucose uptake in cultured hippocampal astrocytes following 7 days of exposure to beta 25-35. Astrocytic glutamate uptake was studied at 1, 5, 10, 15, 20, and 60 min following the addition of [H-3]glutamate (5 nM) to the culture media, and astrocytic glucose uptake was assessed at 60 min after the addition of [C-14]glucose (600 and 640 nM) to the media. Glutamate uptake by control astrocytes was time-dependent. Astrocytes exposed to beta 25-35, however, showed significantly lower glutamate uptake at all sampling times. Similarly, [C-14]glucose uptake by astrocytes was inhibited by beta 25-35. When glucose uptake was blocked by phloretin (10 mM), astrocytic [H-3]glutamate uptake was also blocked, suggesting that the inhibitory effect of beta-amyloid on glutamate uptake is caused by diminished glucose uptake. Thus, our present study suggests a possible link between two proposed mechanisms of pathogenesis of the Alzheimer's disease: glutamate neurotoxicity and global defect in cerebral energy metabolism. (C) 1997 Elsevier Science B.V.