Astrocyte-Neuron Metabolic Pathways
Functional Energy Metabolism:In vivo 13C-NMR Spectroscopy Evidence for Coupling of Cerebral Glucose Consumption and Gl utamatergic Neuronal ActivitySibson N.R.a · Shen J.b · Mason G.F.c · Rothman D.L.d · Behar K.L.e · Shulman R.G.a
Departments of a Molecular Biophysics and Biochemistry, b Internal Medicine, c Psychiatry, d Diagnostic Radiology and e Neurology, Yale University School of Medicine, Newhaven, Conn., USA
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The use of in vivo 13C nuclear magnetic resonance spectroscopy (NMR) has established the pathways of functional interaction between neurons and astrocytes in the mammalian brain and enabled quantitation of these fluxes. A mathematical model of glutamate, glutamine and ammonia metabolism in the brain has been developed, under the constraints of carbon and nitrogen mass balance, allowing the direct and quantitative comparison of in vivo 13C- and 15N-NMR data. Using this model and 13C-NMR data, the authors have separated the neurotransmitter cycling and detoxification components of glutamine synthesis by measuring the rate of glutamine synthesis under normal and hyperammonaemic conditions in the rat brain cortex in vivo. In addition, the simultaneous measurement of the rates of oxidative glucose metabolism and glutamate neurotransmitter cycling in the rat brain cortex has shown that over a range of EEG activity (from isoelectric up to near-resting levels) the stoichiometry between glucose metabolism and glutamate cycling is close to 1:1. Under mild anesthesia, cortical glucose oxidation coupled to glutamatergic synaptic activity accounts for over 80% of total glucose oxidation. Previously, changes in cerebral glucose metabolism have been taken to indicate alterations in functional activity. These recent in vivo results demonstrate, however, that those changes are, in fact, quantitatively coupled to the crux of functional activity, neurotransmitter release. These findings bear upon a number of hypotheses concerning the neurophysiological basis of brain functional imaging methods.
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