SynthesisJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2022
Glucose sparing by glycogenolysis (GSG) determines the relationship between brain metabolism and neurotransmission.
Synthesis in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05855577 (-Clinical Efficacy of Pharmacological Treatments Targeting Energy Metabolism, Evaluated by Gait Analysis, on Motor Function in Parkinson's Disease Patients), which is not on this map. Cited by 34 papers.
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.
The trial behind it
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.
-Clinical Efficacy of Pharmacological Treatments Targeting Energy Metabolism, Evaluated by Gait Analysis, on Motor Function in Parkinson's Disease Patients
Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Computational Modeling of Neurotransmitter Cycling Predicts Human Brain Glutamate and GABA Dynamics in Response to Acute Administration of Exogenous Ketones.Neurochemical research · 2026Article
- Altering MRI rotating frame relaxations by changing the truncation level of Hyperbolic Secant pulse.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2026Article
- Reversible alterations of brain acetate metabolism associated with alcohol consumption.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Perisynaptic Astrocytic Processes as Communication Hubs and Early Sites of Dysfunction.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- Higher fasting brain glucose is associated with lower gray matter volume in healthy adults.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Glial lactate metabolism and transport in Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- Protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on a yorkshire model of brain injury after traumatic blood loss.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 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
- Role of astrocytes in the pathogenesis of perinatal brain injury.Molecular medicine (Cambridge, Mass.) · 2025Review
- 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
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- A budget for brain metabolic water production by glucose catabolism during rest, rises in activity and sleep.Fluids and barriers of the CNS · 2025Review
- Reduced removal of waste products from energy metabolism takes center stage in human brain aging.Scientific reports · 2025Article
- Challenges of Investigating Compartmentalized Brain Energy Metabolism Using Nuclear Magnetic Resonance Spectroscopy in vivo.Neurochemical research · 2025Review
- Article
- Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Metabolic aspects of genetic ion channel epilepsies.Journal of neurochemistry · 2024Review
- Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.Cells · 2024Review
- Neurological glycogen storage diseases and emerging therapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Over the last two decades, it has been established that glucose metabolic fluxes in neurons and astrocytes are proportional to the rates of the glutamate/GABA-glutamine neurotransmitter cycles in close to 1:1 stoichiometries across a wide range of functional energy demands. However, there is presently no mechanistic explanation for these relationships. We present here a theoretical meta-analysis that tests whether the brain's unique compartmentation of glycogen metabolism in the astrocyte and the requirement for neuronal glucose homeostasis lead to the observed stoichiometries. We found that blood-brain barrier glucose transport can be limiting during activation and that the energy demand could only be met if glycogenolysis supports neuronal glucose metabolism by replacing the glucose consumed by astrocytes, a mechanism we call Glucose Sparing by Glycogenolysis (GSG). The predictions of the GSG model are in excellent agreement with a wide range of experimental results from rats, mice, tree shrews, and humans, which were previously unexplained. Glycogenolysis and glucose sparing dictate the energy available to support neuronal activity, thus playing a fundamental role in brain function in health and disease.
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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.