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How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

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Sonnay, Sarah, Gruetter, Rolf, Duarte, João M. N.·2017·Frontiers in Neuroscience
DOI 10.3389/fnins.2017.00288PMC PMC5445183
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Abstract

Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-20th century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS), several groups have worked on assessing cerebral metabolism in vivo. In this context, 1H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. 1H-[13C] MRS, i.e. indirect detection of signals from 13C-coupled 1H, together with infusion of 13C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e. direct detection of 13C isotopomers), the progress in building adequate mathematical models along with the increase in magnetic field strength now available, render possible detailed compartmentalized metabolic flux characterization. In particular, direct 13C MRS offers more detailed dataset acquisitions and provide information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here we review state-of-the-art MR methods to study brain function and metabolism in vivo, and their contribution to the current understanding of how astrocytic energy metabolism supports glutamatergic activity and cerebral function. In this context, recent data suggests that astrocytic metabolism has been underestimated. Namely, the rate of oxidative metabolism in astrocytes is about half of that in neurons, and it can increase as much as the rate of neuronal metabolism in response to somatosensory stimulation.

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  • If pyruvate is not sufficiently present in mitochondria, glutamate can be used for energy instead.

    “Glutamate is reserved for signal transduction and is normally not used for energy purposes; however, if pyruvate is not sufficiently present in the mitochondria, then glutamate can be used instead (Sonnay et al., 2017).”

    From Toxic Concentrations of Glutamate Induce Ferroptosis without Affecting Mitochondrial Respiration in Rodent Brain Slice Cultures (2026) · cites this paper as Sonnay et al., 2017

    The ‘Brain glucose uptake and metabolism’ section says glutamate can re-enter the TCA cycle and be oxidized for energy. It does not say this happens specifically when mitochondrial pyruvate is insufficient, or that glutamate is normally reserved exclusively for signaling. Its discussion of low acetyl-CoA instead describes pyruvate recycling. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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200 of 211 shown

Cited by

Sorted by citations

Authors
Sonnay, S., Gruetter, R., & Duarte, J. M. N.
Affiliations
École Polytechnique Fédérale de Lausanne (CH)
Corresponding author
Duarte, João M. N.
ORCID
Duarte, João M. N.
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2017-05-26
Volume
11
Pages
288-288
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2017.00288
PMC
PMC5445183
OpenAlex
W2617221538
Cited by
74
References
12
Citations by year
2026: 3 · 2025: 7 · 2024: 2 · 2023: 8 · 2022: 13 · 2021: 12 · 2020: 12 · 2019: 5 · 2018: 8 · 2017: 4
FWCI
1.20
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • National Science Foundation
  • École Polytechnique Fédérale de Lausanne
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (149983, 148250, 149983 to RG)
  • Université de Genève
  • Université de Lausanne
  • Centre d'Imagerie BioMédicale
  • Centre Hospitalier Universitaire Vaudois
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
brain energy metabolism, astrocytes, neuronal activity, glutamatergic neurotransmission, oxidative metabolism, 13C NMR, metabolic flux, brain function, somatosensory stimulation

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