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

Silvia Mangia, Federico Giove, Mauro DiNuzzo

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations


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 c-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.

Original languageEnglish (US)
Pages (from-to)2554-2561
Number of pages8
JournalNeurochemical Research
Issue number11
StatePublished - Nov 2012

Bibliographical note

Funding Information:
Acknowledgments S. M. thanks the grant NIH R01 DK62440 for support. This project was also supported by the National Center for Research Resources (Grant Number P41 RR008079) and the National Institute of Biomedical Imaging and Bioengineering (Grant Number P41 EB015894) of NIH. Additional funding supports to CMRR are: Minnesota Medical Foundation, and P30 NS057091. This work was finally supported by the NIH grant 1UL1RR033183 and KL2 RR033182 from the National Center for Research Resources (NCRR) to the University of Minnesota Clinical and Translational Science Institute (CTSI).


  • Aspartate
  • Glutamate
  • Homeostasis
  • Human brain
  • In vivo studies
  • Malate-aspartate shuttle
  • Neuron-astrocyte interactions
  • Neuronal stimulation
  • Neurotransmission


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