ArticleProceedings of the National Academy of Sciences of the United States of America2017
Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Effects of High-Intensity Interval Training Protocols on Blood Lactate Levels and Cognition in Healthy Adults: Systematic Review and Meta-Regression.Sports medicine (Auckland, N.Z.) · 2023Pooled it
- Mechanisms of Exercise Training in Ameliorating Cognitive Function in Patients With Depression: A Narrative Review of Molecular Targets and Clinical Prescriptions.European journal of sport science · 2026Review
- Roles of lactate and protein lactylation in neurogenesis and neurodegenerative disease.Journal of translational medicine · 2026Review
- A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026Review
- Activity-dependent protein synthesis in neurons requires microglial-metabolic coupling.Cell metabolism · 2026Article
- Physical exercise as a non-pharmacological strategy for ADHD considering neurobiological mechanisms, cognitive benefits, and practical recommendations: a narrative review.European archives of psychiatry and clinical neuroscience · 2026Review
- Exercise training promotes nerve cell repair and regeneration after spinal cord injury.Neural regeneration research · 2026Article
- Hepatic Gluconeogenesis and the Antidepressant Effects of Exercise: A Narrative Review.Metabolites · 2026Review
- Peri-Microvascular Glycogen and Lactate Regulate Capillary Constrictions and Ischemia Outcome in Mice.Journal of neurochemistry · 2026Article
- Glycogen and lactate metabolism in mouse fetal Sertoli cells sustain the germ line.Cell reports · 2026Article
- Carbohydrate Ingestion on Exercise Metabolism and Physical Performance.Endocrine reviews · 2026Review
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Brain Nutrient Sensing: A Unifying Framework.Annual review of physiology · 2026Review
- Metabolic interactions in the brain: the crucial roles of neurons, astrocytes, and microglia in health and disease.Frontiers in neuroscience · 2026Review
- The neuron-astrocyte metabolic unit as a cornerstone of brain energy metabolism in health and disease.Nature metabolism · 2025Review
- Review
- Osteocalcin modulates hippocampal activities and influences glycophagy within astrocytes in a chronic unpredictable mild stress mouse model.Comprehensive psychoneuroendocrinology · 2025Article
- Microglia coordinate activity-dependent protein synthesis in neurons through metabolic coupling.bioRxiv : the preprint server for biology · 2025Article
- Lactate Transport via Glial MCT1 and Neuronal MCT2 Is Not Required for Synchronized Synaptic Transmission in Hippocampal Slices Supplied With Glucose.Journal of neurochemistry · 2025Article
- Interplay Between Aging and Glial Cell Dysfunction: Implications for CNS Health.Life (Basel, Switzerland) · 2025Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.
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