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Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons with lactate

PLoS computational biology, 2018-08, Vol.14 (8), p.e1006392-e1006392 [Peer Reviewed Journal]

2018 Coggan et al 2018 Coggan et al ;ISSN: 1553-7358 ;ISSN: 1553-734X ;EISSN: 1553-7358 ;DOI: 10.1371/journal.pcbi.1006392 ;PMID: 30161133

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  • Title:
    Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons with lactate
  • Author: Coggan, Jay S ; Keller, Daniel ; Calì, Corrado ; Lehväslaiho, Heikki ; Markram, Henry ; Schürmann, Felix ; Magistretti, Pierre J
  • BOUZIER-SORE, Anne-Karine
  • Subjects: Biology and Life Sciences ; Physical Sciences
  • Is Part Of: PLoS computational biology, 2018-08, Vol.14 (8), p.e1006392-e1006392
  • Description: 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.
  • Publisher: United States: Public Library of Science
  • Language: English
  • Identifier: ISSN: 1553-7358
    ISSN: 1553-734X
    EISSN: 1553-7358
    DOI: 10.1371/journal.pcbi.1006392
    PMID: 30161133
  • Source: PLoS (Open access)
    Geneva Foundation Free Medical Journals at publisher websites
    PubMed Central
    Directory of Open Access Journals
    ProQuest Central
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