Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons with lactate

PLoS Computational Biology
Jay S CogganPierre J Magistretti

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 glyc...Continue Reading

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Citations

Jan 25, 2019·Journal of Neuroscience Research·Hajime HiraseYuki Oe
Dec 18, 2019·PloS One·Dimitris G PatsatzisS Mani Sarathy
Oct 6, 2019·Nature Reviews. Neurology·Elena C GrossJean Schoenen
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Jul 23, 2020·Nature Metabolism·Marc ZuendBruno Weber
Mar 16, 2021·Frontiers in Cellular Neuroscience·Jérôme Wahis, Matthew G Holt
Mar 17, 2021·Biological Psychiatry·Amalia Floriou-ServouJohannes Bohacek
Dec 4, 2021·Frontiers in Molecular Neuroscience·Polina ShichkovaDaniel Keller

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Methods Mentioned

BETA
electron microscopy

Software Mentioned

trakEM2
NEURON
ANLS
ilastik

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