Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons
Open accessAbstract
Brain is a highly-oxidative organ, but during activation, glycolytic flux is preferentially up-regulated even though oxygen supply is adequate. The biochemical and cellular basis of metabolic changes during brain activation and the fate of lactate produced within brain are important, unresolved issues central to understanding brain function, brain images, and spectroscopic data. Because in vivo brain imaging studies reveal rapid efflux of labeled glucose metabolites during activation, lactate trafficking among astrocytes and between astrocytes and neurons was examined after devising specific, real-time, sensitive enzymatic fluorescent assays to measure lactate and glucose levels in single cells in adult rat brain slices. Astrocytes have a 2- to 4-fold faster and higher capacity for lactate uptake from extracellular fluid and for lactate dispersal via the astrocytic syncytium compared to neuronal lactate uptake from extracellular fluid or shuttling of lactate to neurons from neighboring astrocytes. Astrocytes can also supply glucose to neurons as well as glucose can be taken up by neurons from extracellular fluid. Astrocytic networks can provide neuronal fuel and quickly remove lactate from activated glycolytic domains, and the lactate can be dispersed widely throughout the syncytium to endfeet along the vasculature for release to blood or other brain regions via perivascular fluid flow.
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Gluconeogenic activity in astrocytes could function to build up a glucose concentration gradient to boost the flow of glucose from astrocytes to neurons.
“This suggests that gluconeogenic activity in astrocytes could function to build up a glucose concentration gradient to boost the flow of glucose from astrocytes to neurons [125].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [125]
The Results section, “Glucose transfer from astrocytes to neurons” (page unavailable), reports glucose transfer from astrocytes to neurons. The Discussion section, “Functional anatomy links transport, syncytial network trafficking, and energetics” (page unavailable), says that a high glucose concentration introduced into an astrocyte created a strong concentration gradient. It does not propose that gluconeogenic activity builds that gradient; the experiment supplied the glucose externally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIf unstimulated tissue in the periphery or within the stimulated region is capable of oxidative metabolism of excess lactate, including its contribution will normalize the OGI.
“For instance, if the unstimulated tissue in the periphery or even within the stimulated region is capable of oxidative metabolism of the excess lactate (Madsen et al., 1999; Gandhi et al., 2009), then including the contribution from this tissue will normalize the OGI.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Gandhi et al., 2009
Both LDH isoforms are rapidly equilibrative.
“however, both isoforms are rapidly equilibrative (as argued by Gandhi et al., 2009; Dienel, 2012; Hertz et al., 2014; Bak and Schousboe, 2017)”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Gandhi et al., 2009
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“For instance, if the unstimulated tissue in the periphery or even within the stimulated region is capable of oxidative metabolism of the excess lactate (Madsen et al., 1999; Gandhi et al., 2009), then including the contribution from this tissue will normalize the OGI.”
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- Authors
- Gandhi, G. K., Cruz, N. F., Ball, K. K., & Dienel, G. A.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- ORCID
- Dienel, Gerald A.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-09-23
- Volume
- 111
- Issue
- 2
- Pages
- 522-536
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC2773544
- OpenAlex
- W2063932219
- Cited by
- 162
- References
- 64
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 5 · 2023: 10 · 2022: 8 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 8 · 2017: 19 · 2016: 8 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 12
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Arkansas
- University of Arkansas for Medical Sciences
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 36728, P30NS047546, R01NS036728, NS47546)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- astrocytes, lactate release, astrocyte-neuron lactate shuttle, brain activation, glycolysis, lactate utilization, neuronal glucose uptake, brain energy metabolism
- MeSH terms
- Animals, Astrocytes, Biological Transport, Cell Communication, Extracellular Space, Fluorescence, Glucose, Inferior Colliculi, Male, Neurons, Organ Culture Techniques, Rats, Wistar, Gap Junctions, Lactic Acid, Rats
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