ArticleProceedings of the National Academy of Sciences of the United States of America2014
Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
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Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.
- Glucose sparing by glycogenolysis (GSG) determines the relationship between brain metabolism and neurotransmission.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Pooled it
- Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease.Brain : a journal of neurology · 2021Trial
- Different brain spatial metabolic patterns characterizing different subtypes of multiple system atrophy.Journal of Parkinson's disease · 2026Article
- Lactate Dehydrogenase Inhibition Reverts the Fatty Acid-Induced Neurotoxic Phenotype of Astrocytes.Glia · 2026Article
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- A Bird's-Eye View of Glycolytic Upregulation in Activated Brain: The Major Fate of Lactate Is Release From Activated Tissue, Not Shuttling to Nearby Neurons.Journal of neurochemistry · 2025Review
- Fueling Brain Inhibition: Integrating GABAergic Neurotransmission and Energy Metabolism.Neurochemical research · 2025Review
- Tufm lactylation regulates neuronal apoptosis by modulating mitophagy in traumatic brain injury.Cell death and differentiation · 2025Article
- APP lysine 612 lactylation ameliorates amyloid pathology and memory decline in Alzheimer's disease.The Journal of clinical investigation · 2025Article
- Distinct reduction in relative microglial glucose uptake compared to astrocytes and neurons upon isolation from the brain environment.Frontiers in cellular neuroscience · 2025Article
- Brain network pathophysiology in dystonia.Dystonia (Lausanne, Switzerland) · 2025Article
- Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.Cells · 2024Review
- Effects of a Diabetic Microenvironment on Neurodegeneration: Special Focus on Neurological Cells.Brain sciences · 2024Review
- Electro-metabolic signaling.The Journal of general physiology · 2024Article
- Astrocyte Regulation of Neuronal Function and Survival in Stroke Pathophysiology.Advances in neurobiology · 2024Review
- Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study.Molecular autism · 2023Article
- High-physiological and supra-physiological 1,2-Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- A functional account of stimulation-based aerobic glycolysis and its role in interpreting BOLD signal intensity increases in neuroimaging experiments.Neuroscience and biobehavioral reviews · 2023Review
- Mechanistic multiscale modelling of energy metabolism in human astrocytes reveals the impact of morphology changes in Alzheimer's Disease.PLoS computational biology · 2023Article
- Visualizing reactive astrocyte-neuron interaction in Alzheimer's disease using 11C-acetate and 18F-FDG.Brain : a journal of neurology · 2023Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Previous (13)C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.
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