ArticlePLoS computational biology2018
Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons with lactate.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- Ultrastructure of astrocytes using volume electron microscopy: A scoping review.The Journal of physiology · 2026Article
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Lactate and cognition: a dual modulator.Frontiers in molecular neuroscience · 2026Review
- A 3D-1D-0D multiscale model of the neuro-glial-vascular unit for synaptic and vascular dynamics in the dorsal vagal complex.Journal of mathematical biology · 2025Article
- Old player, new roles: defining the role of the plastidial phosphorylase.The New phytologist · 2025Review
- Sex-dimorphic betaScientific reports · 2025Article
- Myelination selectively modulates BOLD signal in white matter.Research square · 2025Article
- Adenosine ABiological psychiatry · 2025Article
- Seizure and redox rescue in a model of glucose transport deficiency.PLoS computational biology · 2025Article
- Astrocyte involvement in metabolic regulation and disease.Trends in endocrinology and metabolism: TEM · 2025Review
- Elevated locus coeruleus metabolism provides resilience against cognitive decline in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.Cells · 2024Review
- Metabolic Reprogramming of Astrocytes in Pathological Conditions: Implications for Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Centripetal integration of past events in hippocampal astrocytes regulated by locus coeruleus.Nature neuroscience · 2024Article
- Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression.eLife · 2024Article
- Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches.Journal of medical biochemistry · 2024Article
- Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease.Handbook of experimental pharmacology · 2024Review
- Astrocyte regulation of extracellular space parameters across the sleep-wake cycle.Frontiers in cellular neuroscience · 2024Review
- Mechanistic multiscale modelling of energy metabolism in human astrocytes reveals the impact of morphology changes in Alzheimer's Disease.PLoS computational biology · 2023Article
Corrections and comments
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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
The mechanism of rapid energy supply to the brain, especially to accommodate the heightened metabolic activity of excited states, is not well-understood. We explored the role of glycogen as a fuel source for neuromodulation using the noradrenergic stimulation of glia in a computational model of the neural-glial-vasculature ensemble (NGV). The detection of norepinephrine (NE) by the astrocyte and the coupled cAMP signal are rapid and largely insensitive to the distance of the locus coeruleus projection release sites from the glia, implying a diminished impact for volume transmission in high affinity receptor transduction systems. Glucosyl-conjugated units liberated from glial glycogen by NE-elicited cAMP second messenger transduction winds sequentially through the glycolytic cascade, generating robust increases in NADH and ATP before pyruvate is finally transformed into lactate. This astrocytic lactate is rapidly exported by monocarboxylate transporters to the associated neuron, demonstrating that the astrocyte-to-neuron lactate shuttle activated by glycogenolysis is a likely fuel source for neuromodulation and enhanced neural activity. Altogether, the energy supply for both astrocytes and neurons can be supplied rapidly by glycogenolysis upon neuromodulatory stimulus.
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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.