Reversible shifts in the Ca²⁺‐dependent release of aspartate and glutamate from hippocampal slices with changing glucose concentrations

Abstract

It is known that low glucose concentrations increase the aspartate and decrease the glutamate content of brain tissue both in vivo and in vitro. To see whether these changes occur in the transmitter compartment or not, the release of aspartate and glutamate evoked by electrical-field stimulation or by high K+ was followed in slices of rat hippocampus superfused with 5 or 0.2 mM glucose. Superfusion with 0.2 mM glucose increased the evoked release of aspartate about ten times and that of glutamate about threefold. This shift in the ratio of aspartate to glutamate released was accompanied by a similar increase in the relative amount of aspartate contained in the slices. The high evoked release of aspartate and glutamate was well maintained, provided 0.5 mM glutamine was added to the medium. Changing the concentration of glucose after the first period of stimulation rapidly altered the relative amounts of aspartate and glutamate released but not the enhanced release of glutamate. The large evoked release of both aspartate and glutamate in 0.2 mM glucose was almost entirely Ca2+-dependent. The relative amounts of aspartate and glutamate released by 50 mM K+ also changed when the glucose concentration was reduced. Results suggest two effects of low glucose concentrations: an increase in the overflow of synaptically released glutamate due to a decreased uptake and an increase in the proportion of aspartate to glutamate formed and released from the transmitter pool. These observations are consistent with the interpretation that these two transmitters can be released in different proportions from the same terminals.

Low‐affinity excitatory amino acid uptake in hippocampal astrocytes: A possible role of Na+/dicarboxylate cotransporters

“…Interestingly, we found that astrocytes were able to take up D-aspartate through the ''low-affinity'' system under conditions that mimic high synaptic activity or brain pathology. Interestingly, under these conditions the release of aspartate seems to increase relative to that of glutamate (Gundersen et al, 1998(Gundersen et al, , 2001Szerb and O'Regan, 1987;Szerb, 1988), further supporting the view that the ''low-affinity'' uptake sites studied by us could be most important for uptake of aspartate. This notwithstanding, the main function of the dicarboxylate transporters is not likely to be ''low-affinity'' uptake of excitatory amino acids, but uptake of dicarboxylates for metabolic purposes.…”

Aspartate Release and Signalling in the Hippocampus

“…Release studies also indicated that aspartate release is favored relative to glutamate release by prolonged highfrequency stimulation [37] and a low extracellular glucose concentration [37,39,40,56,57]. We took advantage of these features of synaptosomal aspartate release and the distinct antagonist pharmacology of NR1-NR2B NMDA receptors to search for a potential aspartate-mediated response at Schaffer collateral synapses in organotypic hippocampal slice cultures [58].…”

Glutamine as an energy substrate in cultured neurons during glucose deprivation

“…Therefore, their reactions to metabolic insults per se is limited, but experiments using cerebrocortical synaptosomes have shown an increased flux from glutamine to aspartate during glucose deprivation (Yudkoff et al, 1994; Sonnewald and McKenna, 2002), a reaction providing a considerable amount of energy. Brain slice experiments also have suggested that hippocampal neurons during hypoglycemia can metabolize glutamate or glutamine to aspartate (Szerb and O'Regan, 1987). Moreover, recent experiments have indicated that exogenous glutamine is a well‐suited substrate to replenish tricarboxylic acid (TCA) cycle intermediates in cultures of cerebral cortical neurons (Shokati et al, 2005).…”