Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline
Open accessAbstract
Lactate is a versatile metabolite with important roles in modulation of brain glucose utilization rate (CMRglc), diagnosis of brain-injured patients, redox- and receptor-mediated signaling, memory, and alteration of gene transcription. Neurons and astrocytes release and accumulate lactate using equilibrative monocarboxylate transporters that carry out net transmembrane transport of lactate only until intra- and extracellular levels reach equilibrium. Astrocytes have much faster lactate uptake than neurons and shuttle more lactate among gap junction-coupled astrocytes than to nearby neurons. Lactate diffusion within syncytia can provide precursors for oxidative metabolism and glutamate synthesis and facilitate its release from endfeet to perivascular space to stimulate blood flow. Lactate efflux from brain during activation underlies the large underestimation of CMRglc with labeled glucose and fall in CMRO2/CMRglc ratio. Receptor-mediated effects of lactate on locus coeruleus neurons include noradrenaline release in cerebral cortex and c-AMP-mediated stimulation of astrocytic gap junctional coupling, thereby enhancing its dispersal and release from brain. Lactate transport is essential for its multifunctional roles.
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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 Hertz et al., 2014
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Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
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“This led to the proposal of mainly unidirectional flux from astrocytes to neurons; however, both isoforms are rapidly equilibrative (as argued by Gandhi et al., 2009; Dienel, 2012; Hertz et al., 2014; Bak and Schousboe, 2017), and recent single-cell transcriptomics studies show roughly equal expression of the two isof…”
BackgroundDienel, G. A. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24015 · Cited by 168 · see citing works
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- Authors
- Hertz, L., Gibbs, M. E., & Dienel, G. A.
- Affiliations
- China Medical University (CN)
- Monash University (AU)
- University of Arkansas for Medical Sciences (US)
- Corresponding author
- Dienel, Gerald A.
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2014-09-09
- Volume
- 8
- Pages
- 261-261
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC4158791
- OpenAlex
- W2162720163
- Cited by
- 58
- References
- 115
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 6 · 2022: 2 · 2021: 6 · 2019: 4 · 2018: 8 · 2017: 6 · 2016: 4 · 2015: 12 · 2014: 3
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- lactate, astrocytes, electrical coupling, norepinephrine, lactate transport, monocarboxylate transporters, cerebral metabolic rate of glucose, syncytia, glutamate release, blood flow, locus coeruleus, cAMP signaling, brain energy metabolism
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