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13 C MRS studies of neuroenergetics and neurotransmitter cycling in humans
Open accessAbstract
In the last 25 years, 13 C MRS has been established as the only noninvasive method for the measurement of glutamate neurotransmission and cell‐specific neuroenergetics. Although technically and experimentally challenging, 13 C MRS has already provided important new information on the relationship between neuroenergetics and neuronal function, the energy cost of brain function, the high neuronal activity in the resting brain state and how neuroenergetics and neurotransmitter cycling are altered in neurological and psychiatric disease. In this article, the current state of 13 C MRS as it is applied to the study of neuroenergetics and neurotransmitter cycling in humans is reviewed. The focus is predominantly on recent findings in humans regarding metabolic pathways, applications to clinical research and the technical status of the method. Results from in vivo 13 C MRS studies in animals are discussed from the standpoint of the validation of MRS measurements of neuroenergetics and neurotransmitter cycling, and where they have helped to identify key questions to address in human research. Controversies concerning the relationship between neuroenergetics and neurotransmitter cycling and factors having an impact on the accurate determination of fluxes through mathematical modeling are addressed. We further touch upon different 13 C‐labeled substrates used to study brain metabolism, before reviewing a number of human brain diseases investigated using 13 C MRS. Future technological developments are discussed that will help to overcome the limitations of 13 C MRS, with special attention given to recent developments in hyperpolarized 13 C MRS. Copyright © 2011 John Wiley & Sons, Ltd.
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“13 C MRS is presently the only method that provides direct dynamic measurements of glutamate-glutamine cycling in the human brain [10].”
From The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects (2018) · cites this paper as [10]
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“Carbon-13 magnetic resonance spectroscopy ( 13 C MRS) is a unique, noninvasive method to measure neurotransmitter cycling and cell-specific neuroenergetics [8][9][10].”
From The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects (2018) · cites this paper as [10]
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“Accordingly, the glutamate enrichment primarily reflects oxidative energy production through the TCA cycle, while the rate of glutamine enrichment primarily reflects glutamate neurotransmitter cycling [8,10].”
From The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects (2018) · cites this paper as [10]
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How cancer metabolism is tuned for proliferation and vulnerable to disruption
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Brain Glucose Metabolism: Integration of Energetics with Function
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Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo
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Andersen, J. V., Markussen, K. H., Jakobsen, E., Schousboe, A., Waagepetersen, H. S., Rosenberg, P. A., & Aldana, B. I. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108719 · Cited by 392
Metadata
- Authors
- Rothman, D. L., De Feyter, H. M., de Graaf, R. A., Mason, G. F., & Behar, K. L.
- Affiliations
- Yale University (US)
- Department of Diagnostic Radiology, Magnetic Resonance Research Center Yale University School of Medicine New Haven CT USA
- Corresponding author
- Rothman, Douglas L.
- Venue
- NMR in Biomedicine
- Publisher
- Wiley
- Published
- 2011-08-31
- Volume
- 24
- Issue
- 8
- Pages
- 943-957
- ISSN
- 0952-3480 (ISSN-L)
- 1099-1492
- PMC
- PMC3651027
- OpenAlex
- W2147937603
- Cited by
- 290
- References
- 156
- Citations by year
- 2026: 18 · 2025: 16 · 2024: 17 · 2023: 11 · 2022: 15 · 2021: 40 · 2020: 14 · 2019: 16 · 2018: 21 · 2017: 26 · 2016: 27 · 2015: 14 · 2014: 24 · 2013: 20 · 2012: 10
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- NMR in Biomedicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1r01mh095104-01, R01-EB000473)
- National Institute on Alcohol Abuse and Alcoholism (R21AA018210, R21AA019803)
- National Institute on Aging (R01AG034953)
- National Institute of Mental Health (R01-MH95104, R01-MH095104)
- National Institute on Drug Abuse (R01DA021785)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK027121)
- National Institute of Neurological Disorders and Stroke (P30NS052519)
- National Institute of Biomedical Imaging and Bioengineering (R01EB000473, R01EB009336, R41EB008296)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- 13C NMR, neuroenergetics, glutamatergic neurotransmission, brain energy metabolism, metabolic flux, hyperpolarized 13C, 13C-labeled substrates, brain disorders, resting-state brain activity, in vivo brain metabolism
- MeSH terms
- Aging, Alzheimer Disease, Animals, Brain, Carbon Isotopes, Citric Acid Cycle, Energy Metabolism, Glutamine, Humans, Neurons, Magnetic Resonance Spectroscopy, Neurotransmitter Agents, Glutamic Acid
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