β-amyloid 25-35 peptide reduces the expression of glutamine transporter SAT1 in cultured cortical neurons

beta-Amyloid (A beta) peptides may cause malfunction and death of neurons in Alzheimer's disease. We investigated the effect of A beta on key transporters of amino acid neurotransmission in cells cultured from rat cerebral cortex. The cultures were treated with A beta(25-35) at 3 and 10 mu M for 12 and 24 h followed by quantitative analysis of immunofluorescence intensity. In mixed neuronal-glial cell cultures (from P1 rats), A beta reduced the concentration of system A glutamine transporter 1 (SAT1), by up to 50% expressed relative to the neuronal marker microtubule-associated protein 2 (MAP2) in the same cell. No significant effects were detected on vesicular glutamate transporters VGLUT1 or VGLUT2 in neurons, or on glial system N glutamine transporter 1 (SN1). In neuronal cell cultures (from E18 rats), A beta(25-35) did not reduce SAT1 immunoreactivity, suggesting that the observed effect depends on the presence of astroglia. The results indicate that A beta may impair neuronal function and transmitter synthesis, and perhaps reduce excitotoxicity, through a reduction in neuronal glutamine uptake.