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Glutamate-induced metabolic response in astrocytes is caused by an elevation of intracellular sodium via the glutamate transporter GLAST

Glutamate-induced metabolic response in astrocytes is caused by an elevation of intracellular sodium via the glutamate transporter GLAST

Society for Neuroscience Abstracts 27(1): 1029

Glutamate enhances glucose utilization and lactate formation in primary cultures of mouse cortical astrocytes. This effect is mediated by glutamate uptake although we ignore which glutamate transporter is involved and what is the signal that triggers the metabolic response. We have taken advantage of knockout mice for the two glial glutamate transporters, GLAST and GLT-1, to explore this issue in cultured astrocytes. A significant decrease in glutamate uptake was observed in astrocytes from GLAST +/- (-25%) and -/- (-60%) mice vs wildtype. No difference was observed in astrocytes from GLT-1 +/- and -/- vs +/+ mice. An elevation of 11.1+-1.2 mM in (Na+)i was obtained in astrocytes from GLAST +/+ mice upon exposure to 100 muM glutamate. This elevation was reduced to 4.8+-1.2 and 1.1+-0.1 mM in astrocytes from +/- and -/- mice respectively. In contrast, the (Na+)i response remained unchanged between astrocytes from GLT-1 +/+, +/- and -/- mice. When glucose utilization and lactate release were monitored in response to glutamate, a parallel decrease of apprx50% in both responses was seen in astrocytes from GLAST +/- mice while they were abolished in astrocytes from -/- mice. Again, both metabolic responses were similar between astrocytes from GLT-1 +/+, +/- and -/- mice. Our results demonstrate that glutamate transport via GLAST is required for glutamate to produce its metabolic effect. Moreover, it suggests that the elevation in (Na+)i represents the signal triggering the enhancement in aerobic glycolysis.

Accession: 034997896

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