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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 82 (2002), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Transport and metabolism of dicarboxylates may be important in the glial-neuronal metabolic interplay. Further, exogenous dicarboxylates have been suggested as cerebral energy substrates. After intrastriatal injection of [14C]fumarate or [14C]malate, glutamine attained a specific activity 4.1 and 2.6 times higher than that of glutamate, respectively, indicating predominantly glial uptake of these four-carbon dicarboxylates. In contrast, the three-carbon dicarboxylate [14C]malonate gave a specific activity in glutamate which was approximately five times higher than that of glutamine, indicating neuronal uptake of malonate. Therefore, neurones and glia take up different types of dicarboxylates, probably by different transport mechanisms. Labelling of alanine from [14C]fumarate and [14C]malate demonstrated extensive malate decarboxylation, presumably in glia. Intravenous injection of 75 µmol [U-13C]fumarate rapidly led to high concentrations of [U-13C]fumarate and [U-13C]malate in serum, but neither substrate labelled cerebral metabolites as determined by 13C NMR spectroscopy. Only after conversion of [U-13C]fumarate into serum glucose was there 13C-labelling of cerebral metabolites, and only at 〈10% of that obtained with 75 µmol [3-13C]lactate or [2-13C]acetate. These findings suggest a very low transport capacity for four-carbon dicarboxylates across the blood–brain barrier and rule out a role for exogenous fumarate as a cerebral energy substrate.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Glycerol is effective in the treatment of brain oedema but it is unclear if this is due solely to osmotic effects of glycerol or whether the brain may metabolize glycerol. We found that intracerebral injection of [14C]glycerol in rat gave a higher specific activity of glutamate than of glutamine, indicating neuronal metabolism of glycerol. Interestingly, the specific activity of GABA became higher than that of glutamate. NMR spectroscopy of brains of mice given 150 µmol [U-13C]glycerol (0.5 m i.v.) confirmed this predominant labelling of GABA, indicating avid glycerol metabolism in GABAergic neurones. Uptake of [14C]glycerol into cultured cerebellar granule cells was inhibited by Hg2+, suggesting uptake through aquaporins, whereas Hg2+ stimulated glycerol uptake into cultured astrocytes. The neuronal metabolism of glycerol, which was confirmed in experiments with purified synaptosomes and cultured cerebellar granule cells, suggested neuronal expression of glycerol kinase and some isoform of glycerol-3-phosphate dehydrogenase. Histochemically, we demonstrated mitochondrial glycerol-3-phosphate dehydrogenase in neurones, whereas cytosolic glycerol-3-phosphate dehydrogenase was three to four times more active in white matter than in grey matter, reflecting its selective expression in oligodendroglia. The localization of mitochondrial and cytosolic glycerol-3-phosphate dehydrogenases in different cell types implies that the glycerol-3-phosphate shuttle is of little importance in the brain.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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