Neuron-glia metabolic coupling: Role in plasticity and neuroprotection

Handle URI:
http://hdl.handle.net/10754/626323
Title:
Neuron-glia metabolic coupling: Role in plasticity and neuroprotection
Authors:
Magistretti, Pierre J. ( 0000-0002-6678-320X )
Abstract:
A tight metabolic coupling between astrocytes and neurons is a key feature of brain energy metabolism (Magistretti and Allaman, Neuron, 2015). Over the years we have described two basic mechanisms of neurometabolic coupling. First the glycogenolytic effect of VIP and of noradrenaline indicating a regulation of brain homeostasis by neurotransmitters acting on astrocytes, as glycogen is exclusively localized in these cells. Second, the glutamate-stimulated aerobic glycolysis in astrocytes. Both the VIP-and noradrenaline-induced glycogenolysis and the glutamate-stimulated aerobic glycolysis result in the release of lactate from astrocytes as an energy substrate for neurons (Magistretti and Allaman, Neuron, 2015). We have recently shown that lactate is necessary not only as an energy substrate but is also a signaling molecule for long-term memory consolidation and for maintenance of LTP (Suzuki et al, Cell, 2011). At the molecular level we have found that L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, Zif268 and BDNF through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2 (Yang et al, PNAS, 2014). L-lactate potentiates NMDA receptor-mediated currents and the ensuing increases in intracellular calcium. These results reveal a novel action of L-lactate as a signaling molecule for neuronal plasticity. We have also recently shown that peripheral administration of lactate exerts antidepressant-like effects in three animal models of depression (Carrard et al, Mol.Psy., 2016).
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program
Citation:
Magistretti P (2017) Neuron-glia metabolic coupling: Role in plasticity and neuroprotection. Journal of the Neurological Sciences 381: 24. Available: http://dx.doi.org/10.1016/j.jns.2017.08.107.
Publisher:
Elsevier BV
Journal:
Journal of the Neurological Sciences
Issue Date:
2-Dec-2017
DOI:
10.1016/j.jns.2017.08.107
Type:
Presentation
ISSN:
0022-510X
Additional Links:
http://www.sciencedirect.com/science/article/pii/S0022510X17306044
Appears in Collections:
Bioscience Program; Presentations; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorMagistretti, Pierre J.en
dc.date.accessioned2017-12-07T13:16:39Z-
dc.date.available2017-12-07T13:16:39Z-
dc.date.issued2017-12-02en
dc.identifier.citationMagistretti P (2017) Neuron-glia metabolic coupling: Role in plasticity and neuroprotection. Journal of the Neurological Sciences 381: 24. Available: http://dx.doi.org/10.1016/j.jns.2017.08.107.en
dc.identifier.issn0022-510Xen
dc.identifier.doi10.1016/j.jns.2017.08.107en
dc.identifier.urihttp://hdl.handle.net/10754/626323-
dc.description.abstractA tight metabolic coupling between astrocytes and neurons is a key feature of brain energy metabolism (Magistretti and Allaman, Neuron, 2015). Over the years we have described two basic mechanisms of neurometabolic coupling. First the glycogenolytic effect of VIP and of noradrenaline indicating a regulation of brain homeostasis by neurotransmitters acting on astrocytes, as glycogen is exclusively localized in these cells. Second, the glutamate-stimulated aerobic glycolysis in astrocytes. Both the VIP-and noradrenaline-induced glycogenolysis and the glutamate-stimulated aerobic glycolysis result in the release of lactate from astrocytes as an energy substrate for neurons (Magistretti and Allaman, Neuron, 2015). We have recently shown that lactate is necessary not only as an energy substrate but is also a signaling molecule for long-term memory consolidation and for maintenance of LTP (Suzuki et al, Cell, 2011). At the molecular level we have found that L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, Zif268 and BDNF through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2 (Yang et al, PNAS, 2014). L-lactate potentiates NMDA receptor-mediated currents and the ensuing increases in intracellular calcium. These results reveal a novel action of L-lactate as a signaling molecule for neuronal plasticity. We have also recently shown that peripheral administration of lactate exerts antidepressant-like effects in three animal models of depression (Carrard et al, Mol.Psy., 2016).en
dc.publisherElsevier BVen
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0022510X17306044en
dc.rightsArchived with thanks to Journal of the Neurological Sciences.en
dc.titleNeuron-glia metabolic coupling: Role in plasticity and neuroprotectionen
dc.typePresentationen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentBioscience Programen
dc.identifier.journalJournal of the Neurological Sciencesen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionEPFL, Switzerlanden
kaust.authorMagistretti, Pierre J.en
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