Metabolic pathways and activity-dependent modulation of glutamate concentration in the human brain

Mangia, Silvia; Giove, Federico; DiNuzzo, Mauro

doi:10.1007/s11064-012-0848-4

Cited by 90Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismAdvanced MRI Techniques and Applications

Metabolic pathways and activity-dependent modulation of glutamate concentration in the human brain

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Mangia, Silvia, Giove, Federico, DiNuzzo, Mauro·2012·Neurochemical Research

DOI 10.1007/s11064-012-0848-4PMC PMC3489977

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Abstract

Glutamate is one of the most versatile molecules present in the human brain, involved in protein synthesis, energy production, ammonia detoxification, and transport of reducing equivalents. Aside from these critical metabolic roles, glutamate plays a major part in brain function, being not only the most abundant excitatory neurotransmitter, but also the precursor for γ-aminobutyric acid, the predominant inhibitory neurotransmitter. Regulation of glutamate levels is pivotal for normal brain function, as abnormal extracellular concentration of glutamate can lead to impaired neurotransmission, neurodegeneration and even neuronal death. Understanding how the neuron-astrocyte functional and metabolic interactions modulate glutamate concentration during different activation status and under physiological and pathological conditions is a challenging task, and can only be tentatively estimated from current literature. In this paper, we focus on describing the various metabolic pathways which potentially affect glutamate concentration in the brain, and emphasize which ones are likely to produce the variations in glutamate concentration observed during enhanced neuronal activity in human studies.

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Increased glutamate levels reflect an upregulation of the MAS.
“Our results can be interpreted in keeping with the concept that increased glutamate levels reflect an upregulation of the MAS (Mangia et al., 2012), although we were unable to report significant differences in aspartate levels likely due to insufficient sensitivity of MRS at 3T.”
From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as Mangia et al., 2012
The Conclusion links increased glutamate to a rise in overall MAS activity when it is accompanied by a matched decrease in aspartate. It also says glutamate increases without a matching aspartate decrease may arise from de novo synthesis. Because the citing authors could not establish an aspartate change, the source does not support treating their glutamate increase alone as evidence of MAS upregulation. (LLM, conf=0.88)
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Authors: Mangia, S., Giove, F., & DiNuzzo, M.
Affiliations: University of Minnesota (US)
Centro Ricerche Enrico Fermi (IT)
Corresponding author: Mangia, Silvia
ORCID: Mangia, Silvia
Giove, Federico
DiNuzzo, Mauro
Venue: Neurochemical Research
Publisher: Springer Science and Business Media LLC
Published: 2012-07-31
Volume: 37
Issue: 11
Pages: 2554-2561
ISSN: 0364-3190 (ISSN-L)
1573-6903
DOI: 10.1007/s11064-012-0848-4
PMC: PMC3489977
OpenAlex: W2005342660
Cited by: 90
References: 61
Citations by year: 2026: 9 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 9 · 2020: 5 · 2019: 3 · 2018: 11 · 2017: 7 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 7
FWCI: 0.60
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Neurochemical Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R01DK062440)
National Institute of Neurological Disorders and Stroke (P30NS057091)
National Institute of Biomedical Imaging and Bioengineering (P41EB015894)
National Center for Research Resources (KL2RR033182, UL1RR033183, P41RR008079)
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: glutamate metabolism, astrocyte-neuron interaction, brain energy metabolism, ammonia detoxification, glutamate uptake, neuronal activity, excitatory neurotransmission, GABA synthesis, neurodegeneration, human brain
MeSH terms: Astrocytes, Brain, Homeostasis, Humans, Synaptic Transmission, Neurons, Glutamic Acid

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Metabolic pathways and activity-dependent modulation of glutamate concentration in the human brain

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