Using 13C labeled compounds and 13C magnetic resonance spectroscopy (MRS) it is possible to monitor cellular metabolism and astrocyte-neuronal interactions. Various 13C labeled substrates are used to unravel different aspects of cerebral metabolism. This presentation will focus on [1-13C]glucose, [U-13C] glucose, [2-13C]glucose and [3-13C]glucose metabolism in cerebellar and cerebro-cortical neurons and astrocytes in culture. [1-13C]Glucose is metabolized by both astrocytes and neurons and labeling of metabolites from this isotopomer of glucose will not be affected by the pentose phosphate pathway (PPP). Using [U-13C]glucose and 3-nitropropionic acid it could be confirmed that pyruvate carboxylation takes place in cortical astrocytes but not neurons. This carboxylation leads to the formation of oxaloacetate, which condenses with acetyl coenzyme A to form citrate. However, oxaloacetate may also be converted to malate and fumarate before being regenerated. This redundant pathway is termed the oxaloacetate-fumarate-flux, or backflux and has been shown to be extensive using [2-13C]- and [3-13C]glucose in cultured cerebral cortical and cerebellar cultures. It could also be calculated to be present in vivo. [2-13C]- and [3-13C]glucose can also be used to probe the PPP in neurons where pyruvate carboxylation is not present. Indeed, the PPP contributed to labeling of glutamate and other metabolites.
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Cerebral metabolism of glucose, one of the determinants of tissue ATP level, is crucial for the CNS function. The activity of P-type pumps: Na+, K+-ATPase, Ca+2-ATPase and Mg+2-ATPase were examined in rat brain synaptosomes to determine if changes in the enzyme activity related to aging are potentially associated with alterations in glucose homeostasis. Male Wistar rats (newborn, 3- and 18-month-old) were sacrificed by decapitation and synaptic plasma membranes were isolated from brains. In vivo study demonstrated that 18-month-old rats were characterized by hyperglycemia, hyperinsulinemia and increased total antyoxidative status (TAS) level. These conditions had a different impact on activities of the ATPases tested in vivo: only the activity of Ca+2-ATPase decreased whereas that of Mg+2-ATPase increased significantly. In vitro experiments, prior incubation of isolated synaptosomes with glucose of concentrations corresponding to normoglycemia in vivo (4.5 - 6.5 mM), stimulated Ca+2-ATPase activity, whereas higher glucose concentrations (10.0 - 12.5 mM) inhibited significantly the enzyme activity. The most sensitive to hyperglycemia appeared Na+, K+-ATPase in old rats synaptosomes with the progressive decline starting at 6.5 mM glucose. The activity of Mg+2-ATPase was not inhibited in vitro even at high glucose concentrations that may explain the increased in vivo, activity of this enzyme in old, hyperglycemic rats.
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