title: In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics.
abstract: In this article we review recent studies, primarily from our laboratory, using 13C NMR (nuclear magnetic resonance) to non-invasively measure the rate of the glutamate-glutamine neurotransmitter cycle in the cortex of rats and humans. In the glutamate-glutamine cycle, glutamate released from nerve terminals is taken up by surrounding glial cells and returned to the nerve terminals as glutamine. 13C NMR studies have shown that the rate of the glutamate-glutamine cycle is extremely high in both the rat and human cortex, and that it increases with brain activity in an approximately 1:1 molar ratio with oxidative glucose metabolism. The measured ratio, in combination with proposals based on isolated cell studies by P. J. Magistretti and co-workers, has led to the development of a model in which the majority of brain glucose oxidation is mechanistically coupled to the glutamate-glutamine cycle. This model provides the first testable mechanistic relationship between cortical glucose metabolism and a specific neuronal activity. We review here the experimental evidence for this model as well as implications for blood oxygenation level dependent magnetic resonance imaging and positron emission tomography functional imaging studies of brain function.
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Rothman
authors.forename: N R
authors.initials: NR
authors.lastname: Sibson
authors.forename: F
authors.initials: F
authors.lastname: Hyder
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.forename: K L
authors.initials: KL
authors.lastname: Behar
authors.forename: R G
authors.initials: RG
authors.lastname: Shulman
mesh_terms: D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000378:metabolism; D009587:Nitrogen Isotopes; D051381:Rats; D014055:Tomography, Emission-Computed
chemical_list: D002247:Carbon Isotopes; D018377:Neurotransmitter Agents; D009587:Nitrogen Isotopes; D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia; D005947:Glucose