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      Astroglial networking contributes to neurometabolic coupling

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          Abstract

          The strategic position of astrocytic processes between blood capillaries and neurons, provided the early insight that astrocytes play a key role in supplying energy substrates to neurons in an activity-dependent manner. The central role of astrocytes in neurometabolic coupling has been first established at the level of single cell. Since then, exciting recent work based on cellular imaging and electrophysiological recordings has provided new mechanistic insights into this phenomenon, revealing the crucial role of gap junction (GJ)-mediated networks of astrocytes. Indeed, astrocytes define the local availability of energy substrates by regulating blood flow. Subsequently, in order to efficiently reach distal neurons, these substrates can be taken up, and distributed through networks of astrocytes connected by GJs, a process modulated by neuronal activity. Astrocytic networks can be morphologically and/or functionally altered in the course of various pathological conditions, raising the intriguing possibility of a direct contribution from these networks to neuronal dysfunction. The present review upgrades the current view of neuroglial metabolic coupling, by including the recently unravelled properties of astroglial metabolic networks and their potential contribution to normal and pathological neuronal activity.

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          Most cited references45

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          Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation.

          The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization.

            Glutamate, released at a majority of excitatory synapses in the central nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly via Na(+)-dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis--i.e., glucose utilization and lactate production--in astrocytes. This metabolic action is mediated by activation of a Na(+)-dependent uptake system and not by interaction with receptors. The mechanism involves the Na+/K(+)-ATPase, which is activated by an increase in the intracellular concentration of Na+ cotransported with glutamate by the electrogenic uptake system. Thus, when glutamate is released from active synapses and taken up by astrocytes, the newly identified signaling pathway described here would provide a simple and direct mechanism to tightly couple neuronal activity to glucose utilization. In addition, glutamate-stimulated glycolysis is consistent with data obtained from functional brain imaging studies indicating local nonoxidative glucose utilization during physiological activation.
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              Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice.

              Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology.
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                Author and article information

                Journal
                Front Neuroenergetics
                Front Neuroenergetics
                Front. Neuroenergetics
                Frontiers in Neuroenergetics
                Frontiers Media S.A.
                1662-6427
                12 February 2013
                26 April 2013
                2013
                : 5
                : 4
                Affiliations
                [1] 1CEA DSV I2BM MIRCen and CNRS URA2210, Fontenay-aux-Roses Paris, France
                [2] 2Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, CNRS UMR 7241, INSERM U1050, Collège de France Paris, France
                Author notes

                Edited by: Sebastian Cerdan, Instituto de Investigaciones Biomedicas Alberto Sols, Spain

                Reviewed by: Sebastian Cerdan, Instituto de Investigaciones Biomedicas Alberto Sols, Spain; Anne-Karine Bouzier-Sore, CNRSUniversité Victor Segalen, France

                *Correspondence: Nathalie Rouach, Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, CNRS UMR 7241, INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75005 Paris, France. e-mail: nathalie.rouach@ 123456college-de-france.fr
                Article
                10.3389/fnene.2013.00004
                3636502
                23637659
                11fe2eb0-f51a-4aaa-85a2-42d25974ba19
                Copyright © 2013 Escartin and Rouach.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 31 January 2013
                : 18 March 2013
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 63, Pages: 8, Words: 6834
                Categories
                Neuroscience
                Review Article

                Neurosciences
                astrocytes,neuroglial interactions,gap junctions,astroglial networks,energy metabolism,neurometabolic coupling,neurodegenerative diseases,epilepsy

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