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Brain Lactate Is an Obligatory Aerobic Energy Substrate for Functional Recovery After Hypoxia: Further In Vitro Validation
Abstract
This study used the rat hippocampal slice preparation and the monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), to assess the obligatory role that lactate plays in fueling the recovery of synaptic function after hypoxia upon reoxygenation. At a concentration of 500 microM, 4-CIN blocked lactate-supported synaptic function in hippocampal slices under normoxic conditions in 15 min. The inhibitor had no effect on glucose-supported synaptic function. Of control hippocampal slices exposed to 10-min hypoxia, 77.8 +/- 6.8% recovered synaptic function after 30-min reoxygenation. Of slices supplemented with 500 microM 4-CIN, only 15 +/- 10.9% recovered synaptic function despite the large amount of lactate formed during the hypoxic period and the abundance of glucose present before, during, and after hypoxia. These results indicate that 4-CIN, when present during hypoxia and reoxygenation, blocks lactate transport from astrocytes, where the bulk of anaerobic lactate is formed, to neurons, where lactate is being utilized aerobically to support recovery of function after hypoxia. These results unequivocally validate that brain lactate is an obligatory aerobic energy substrate for posthypoxia recovery of function.
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“Subsequently, nu-merous studies have demonstrated that neurons efficiently use lactate as an energy source (Schurr et al., 1997;Bouzier et al., 2000;Qu et al., 2001) and may even prefer it over glucose (Bouzier et al., 2000;Itoh et al., 2003).”
From An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014) · cites this paper as Schurr et al., 1997
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Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875
“Subsequently, nu- merous studies have demonstrated that neurons efficiently use lactate as an energy source (Schurr et al., 1997; Bouzier et al., 2000; Qu et al., 2001) and may even prefer it over glucose (Bouzier et al., 2000; Itoh et al., 2003).”
BackgroundIschemic Cell Death in Brain Neurons
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Nicholls, D. G., & Budd, S. L. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.1.315 · Cited by 1,243
Metadata
- Authors
- Schurr, A., Payne, R. S., Miller, J. J., & Rigor, B. M.
- Affiliations
- University of Louisville (US)
- Pediatrics and Genetics (US)
- Corresponding author
- Schurr, Avital
- ORCID
- Schurr, Avital
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1997-07
- Volume
- 69
- Issue
- 1
- Pages
- 423-426
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1990158364
- Cited by
- 262
- References
- 0
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 8 · 2016: 7 · 2015: 9 · 2014: 16 · 2013: 9 · 2012: 9
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Keywords
- brain lactate, hypoxia, reoxygenation, monocarboxylate transporters, HCCA, hippocampus, astrocytes, lactate transport, aerobic metabolism, glucose utilization
- MeSH terms
- Animals, Brain Chemistry, Coumaric Acids, Electrophysiology, Energy Metabolism, Glucose, Hippocampus, Lactates, Male, Organ Culture Techniques, Synapses, Cell Hypoxia, Rats, Sprague-Dawley, Rats
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