The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo
Open accessAbstract
Previous studies have shown that the glutamate/glutamine (Glu/Gln) neurotransmitter cycle and neuronal glucose oxidation are proportional (1:1), with increasing neuronal activity above isoelectricity. GABA, a product of Glu metabolism, is synthesized from astroglial Gln and contributes to total Glu/Gln neurotransmitter cycling, although the fraction contributed by GABA is unknown. In the present study, we used 13 C NMR spectroscopy together with i.v. infusions of [1,6- 13 C 2 ]glucose and [2- 13 C]acetate to separately determine rates of Glu/Gln and GABA/Gln cycling and their respective tricarboxylic acid cycles in the rat cortex under conditions of halothane anesthesia and pentobarbital-induced isoelectricity. Under 1% halothane anesthesia, GABA/Gln cycle flux comprised 23% of total (Glu plus GABA) neurotransmitter cycling and 18% of total neuronal tricarboxylic acid cycle flux. In isoelectric cortex, glucose oxidation was reduced >3-fold in glutamatergic and GABAergic neurons, and neurotransmitter cycling was below detection. Hence, in both cell types, the primary energetic costs are associated with neurotransmission, which increase together as cortical activity is increased. The contribution of GABAergic neurons and inhibition to cortical energy metabolism has broad implications for the interpretation of functional imaging signals.
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Glutamate and GABA can be utilized as energy metabolites.
“Although glutamate and GABA are mostly known for their roles as neurotransmitters in excitatory and inhibitory neurons, respectively, they can also be utilized as energy metabolites46–49.”
From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [49]
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Self-citation
- Authors
- Patel, A. B., de Graaf, R. A., Mason, G. F., Rothman, D. L., Shulman, R. G., & Behar, K. L.
- Affiliations
- Yale University (US)
- Departments of Diagnostic Radiology, Psychiatry, and Biomedical Engineering, and Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, CT 06520
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-04-04
- Volume
- 102
- Issue
- 15
- Pages
- 5588-5593
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC556230
- OpenAlex
- W2169826322
- Cited by
- 343
- References
- 2
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 5 · 2023: 8 · 2022: 17 · 2021: 16 · 2020: 17 · 2019: 14 · 2018: 18 · 2017: 21 · 2016: 18 · 2015: 15 · 2014: 28 · 2013: 25 · 2012: 14
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA 13430, K02AA013430)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 27121, R01DK027121)
- National Institute of Neurological Disorders and Stroke (NS38413, R01NS034813)
- National Institute of Biomedical Imaging and Bioengineering (EB 002097, R01EB002097)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- GABA, glutamate-glutamine cycle, TCA cycle, GABAergic neurons, glutamatergic neurons, pentobarbital, halothane anesthesia, 13C NMR, functional neuroimaging
- MeSH terms
- Acetates, Amino Acids, Animals, Biological Transport, Blood Glucose, Cerebral Cortex, Energy Metabolism, gamma-Aminobutyric Acid, Glucose, Glutamine, Halothane, Male, Neuroglia, Neurons, Magnetic Resonance Spectroscopy, Oxidation-Reduction, Pentobarbital, Rats, Sprague-Dawley, Anesthetics, Inhalation, Glutamic Acid, GABA Modulators, Rats
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