Cited by 337Advanced MRI Techniques and ApplicationsNeuroscience and Neuropharmacology ResearchAmino Acid Enzymes and Metabolism

In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function

Rothman, Douglas L., Behar, Kevin L., Hyder, Fahmeed, Shulman, Robert G.·2003·Annual Review of Physiology

Abstract

Until very recently, non-invasive measurement of the glutamate-glutamine cycle in the intact mammalian brain had not been possible. In this review, we describe some studies that have led to quantitative assessment of the glutamate-glutamine cycle (Vcyc), as well as other important metabolic fluxes (e.g., glucose oxidation, CMRglc(ox)), with (13)C magnetic resonance spectroscopy (MRS) in vivo. These (13)C MRS studies clearly demonstrate that glutamate released from presynaptic neurons is taken up by the astrocyte for subsequent glutamine synthesis. Contrary to the earlier concept of a small, metabolically inactive neurotransmitter pool, in vivo (13)C MRS studies demonstrate that glutamate release and recycling is a major metabolic pathway that cannot be distinguished from its actions of neurotransmission. Furthermore, the in vivo (13)C MRS studies demonstrate in the rat cerebral cortex that increases in Vcyc and neuronal CMRglc(ox) are linearly related with a close to 1:1 slope. Measurements in human cerebral cortex are in agreement with this result. This relationship is consistent with more than two thirds of the energy yielded by glucose oxidation being used to support events associated with glutamate neurotransmission, and it supports a molecular model of a stoichiometric coupling between glutamate neurotransmission and functional glucose oxidation. (13)C MRS measurements of resting human cerebral cortex have found a high level of glutamate-glutamine cycling. This high resting neuronal activity, which is subtracted away in brain mapping studies by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), has significant implications for the interpretations of functional imaging data. Here we review and discuss the importance of neurotransmission and neuroenergetics as measured by (13)C MRS for understanding brain function and interpreting fMRI.

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Crossref · 10.1146/annurev.physiol.65.092101.142131

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  • The glutamatergic transmission and metabolism are strongly coupled, and findings on glutamate and glutamine levels in schizophrenia could give insight into possible changes in neuronal activity during the course of the disease.

    “Theglutamatergictransmission and metabolism are strongly coupled, and findings on glutamate and glutamine levels in schizophrenia could give an insight in possible changes in neuronal activity during the course of the disease.21”

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Authors
Rothman, D. L., Behar, K. L., Hyder, F., & Shulman, R. G.
Affiliations
Yale University (US)
Venue
Annual Review of Physiology
Published
2003-03
Volume
65
Issue
1
Pages
401-427
ISSN
  • 0066-4278 (ISSN-L)
  • 1545-1585
OpenAlex
W2158402798
Cited by
337
References
122
Citations by year
2026: 10 · 2025: 11 · 2024: 7 · 2023: 5 · 2022: 22 · 2021: 14 · 2020: 18 · 2019: 16 · 2018: 18 · 2017: 12 · 2016: 10 · 2015: 13 · 2014: 15 · 2013: 19 · 2012: 21
FWCI
2.35
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r29ns037203-05)
  • National Institute on Deafness and Other Communication Disorders (DC-003710, R01DC003710)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 27121, R01DK027121)
  • National Institute of Neurological Disorders and Stroke (NS 32126, R29NS032126, NS34813, NS37203, NS-044594, R01NS034813)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD032573, HD32573)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
glutamate-glutamine cycle, glutamatergic neurotransmission, neuroenergetics, 13C NMR, presynaptic glutamate release, resting-state brain activity, cerebral cortex, brain energy metabolism
MeSH terms
Animals, Brain, Cell Communication, Energy Metabolism, Humans, Neuroglia, Neurons, Magnetic Resonance Spectroscopy, Glutamic Acid

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