ReviewJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Is L-lactate a novel signaling molecule in the brain?
Review in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review.Journal of neurochemistry · 2019Pooled it
- Review
- NPAS3-regulated astrocyte mitochondrial bioenergetics is required for cognition.Science advances · 2026Article
- MPTP and rotenone cause dopaminergic neuronal death by increasing DDIT4 promoter lactylation.Acta pharmacologica Sinica · 2026Article
- L-lactic acid enhances type I interferon immune response and inhibits virus infection by promoting IRF9 L-lactylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular L-lactate dynamics.Nature communications · 2025Article
- Regulation of L-Lactate in Glutamate Excitotoxicity Under Cerebral Ischemia: Pathophysiology and Preventive Strategy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Review
- L- and D-Lactate: unveiling their hidden functions in disease and health.Cell communication and signaling : CCS · 2025Review
- A neurometabolic mechanism involving dmPFC/dACC lactate in physical effort-based decision-making.Molecular psychiatry · 2025Article
- Molecular Regulation of Cardiomyocyte Maturation.Current cardiology reports · 2025Review
- Lipid droplets in central nervous system and functional profiles of brain cells containing lipid droplets in various diseases.Journal of neuroinflammation · 2025Review
- Enhancing human strength via neural modulation: mechanisms of maximal voluntary contraction and translational interventions.Frontiers in physiology · 2025Review
- Lactate/Hydroxycarboxylic Acid Receptor 1 in Alzheimer's Disease: Mechanisms and Therapeutic Implications-Exercise Perspective.Molecular neurobiology · 2024Review
- Article
- Neuroprotective role of lactate in a human in vitro model of the ischemic penumbra.Scientific reports · 2024Article
- High-Performance Genetically Encoded Green Fluorescent Biosensors for Intracellular l-Lactate.ACS central science · 2024Article
- S100B Secretion in Astrocytes, Unlike C6 Glioma Cells, Is Downregulated by Lactate.Metabolites · 2023Article
- Major Depressive Disorder and Gut Microbiota: Role of Physical Exercise.International journal of molecular sciences · 2023Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In the brain, L-lactate is produced by both neurons and astrocytes. There is no doubt that neurons use L-lactate as a supplementary fuel although the importance of this energy source is disputed. Irrespective of its caloric value, L-lactate might also have a signaling role in the brain. Here, we review several current hypotheses of L-lactate mediated signaling. Some proposed mechanisms require L-lactate entry into the neurons leading to a shift in ATP/ADP ratio or redox state. Others postulate interaction with either known receptor HCA1 (GPR81) or a novel, yet unidentified receptor. We argue that the sensitivity of any such mechanism has to match the concentration range of extracellular L-lactate, which is less than ~1.5 mmol/L under physiologic conditions. From that point of view, some of the proposed mechanisms require supraphysiologic levels of L-lactate and could be engaged during ischemia or seizures when L-lactate concentration rises dramatically. Currently, we do not know whether L-lactate production in the brain occurs in microdomains, which might create higher than average local concentrations. Nevertheless, it is clear that in the brain, as in the peripheral tissues, L-lactate is not only used as a source of energy but also acts as a signaling molecule.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.