ArticleBrain : a journal of neurology2023
Glycolysis regulates neuronal excitability via lactate receptor, HCA1R.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 29 citations in OpenAlex.
- HCAR1-mediated lactate signaling modulates motor behavior and regulates spontaneous firing in Purkinje cells.iScience · 2026Article
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- Enhanced Glycolysis-Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate metabolism links reactive microglia, amyloid pathology, and Aβ dynamics.Journal of neuroinflammation · 2026Article
- Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lactate receptor HCAR1 in neonatal hypoxic-ischemic seizures.Epilepsia · 2026Article
- Hydroxycarboxylic Acid Receptor 2 Mediates β-hydroxybutyrate's Antiseizure Effect in Mice.Annals of neurology · 2026Article
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells.Frontiers in cell and developmental biology · 2026Article
- Activation of silent synapses driven by emerging technologies: mechanisms, disease associations, and prospects for clinical translation.Frontiers in synaptic neuroscience · 2026Review
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Transcriptomic decoding of regional cortical vulnerability to drug-resistant epilepsy using 7T MRI.Communications biology · 2025Article
- Status epilepticus: Updates on mechanisms and treatments.Epilepsia open · 2025Review
- Coordination acid-engineered Prussian Blue affects glycometabolic reprogramming in microglia for epileptic treatment.Journal of nanobiotechnology · 2025Article
- Astrocytes of the hippocampus and responses to periprandial neuroendocrine hormones.Physiology & behavior · 2025Review
- Hyperpolarized [1-Brain communications · 2025Article
- The Effects of Exercise on Hippocampus-Based Cognitive Dysfunction in Type 2 Diabetes Mellitus: A Possible Involvement of Hippocampal Monocarboxylate Transporter 2.Advances in neurobiology · 2025Review
- Lactylation: A Novel Post-Translational Modification with Clinical Implications in CNS Diseases.Biomolecules · 2024Review
- Article
- Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner.iScience · 2024Article
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5 authors at 1 institution in 1 country.
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Abstract
Repetitively firing neurons during seizures accelerate glycolysis to meet energy demand, which leads to the accumulation of extracellular glycolytic by-product lactate. Here, we demonstrate that lactate rapidly modulates neuronal excitability in times of metabolic stress via the hydroxycarboxylic acid receptor type 1 (HCA1R) to modify seizure activity. The extracellular lactate concentration, measured by a biosensor, rose quickly during brief and prolonged seizures. In two epilepsy models, mice lacking HCA1R (lactate receptor) were more susceptible to developing seizures. Moreover, HCA1R deficient (knockout) mice developed longer and more severe seizures than wild-type littermates. Lactate perfusion decreased tonic and phasic activity of CA1 pyramidal neurons in genetically encoded calcium indicator 7 imaging experiments. HCA1R agonist 3-chloro-5-hydroxybenzoic acid (3CL-HBA) reduced the activity of CA1 neurons in HCA1R WT but not in knockout mice. In patch-clamp recordings, both lactate and 3CL-HBA hyperpolarized CA1 pyramidal neurons. HCA1R activation reduced the spontaneous excitatory postsynaptic current frequency and altered the paired-pulse ratio of evoked excitatory postsynaptic currents in HCA1R wild-type but not in knockout mice, suggesting it diminished presynaptic release of excitatory neurotransmitters. Overall, our studies demonstrate that excessive neuronal activity accelerates glycolysis to generate lactate, which translocates to the extracellular space to slow neuronal firing and inhibit excitatory transmission via HCA1R. These studies may identify novel anticonvulsant target and seizure termination mechanisms.
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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.