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Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission
Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular t...
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Published in: | Science (American Association for the Advancement of Science) 2008-12, Vol.322 (5907), p.1551-1555 |
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description | Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons. |
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However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1164022</identifier><identifier>PMID: 19056987</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Animals ; Astrocytes ; Astrocytes - metabolism ; Biological and medical sciences ; Blood Glucose - metabolism ; Blood vessels ; Cell Membrane Permeability ; Cellular biology ; Connexin 30 ; Connexin 43 - metabolism ; Connexins - metabolism ; Diffusion ; Energy metabolism ; Epilepsy - physiopathology ; Excitatory Postsynaptic Potentials ; Fundamental and applied biological sciences. Psychology ; Gap junctions ; Gap Junctions - physiology ; Glucose - metabolism ; Glutamic Acid - metabolism ; Hippocampus - blood supply ; Hippocampus - cytology ; Hippocampus - physiology ; In Vitro Techniques ; Lactates ; Lactic Acid - metabolism ; Life Sciences ; Metabolic Networks and Pathways ; Metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Molecular biology ; Neurology ; Neurons ; Neurons - physiology ; Neuroscience ; Patch-Clamp Techniques ; Pipettes ; Proteins ; Pyramidal cells ; Receptors, AMPA - metabolism ; Synaptic Transmission ; Vertebrates: nervous system and sense organs</subject><ispartof>Science (American Association for the Advancement of Science), 2008-12, Vol.322 (5907), p.1551-1555</ispartof><rights>Copyright 2008 American Association for the Advancement of Science</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2008, American Association for the Advancement of Science</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c654t-5a724dcc6019649410d6cd97523ffac5d23e9bd2f9953c7fe889ae795dfbf9883</citedby><cites>FETCH-LOGICAL-c654t-5a724dcc6019649410d6cd97523ffac5d23e9bd2f9953c7fe889ae795dfbf9883</cites><orcidid>0000-0002-5574-888X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,2884,2885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20980189$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19056987$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02633838$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Rouach, Nathalie</creatorcontrib><creatorcontrib>Koulakoff, Annette</creatorcontrib><creatorcontrib>Abudara, Veronica</creatorcontrib><creatorcontrib>Willecke, Klaus</creatorcontrib><creatorcontrib>Giaume, Christian</creatorcontrib><title>Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.</description><subject>Animals</subject><subject>Astrocytes</subject><subject>Astrocytes - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Blood vessels</subject><subject>Cell Membrane Permeability</subject><subject>Cellular biology</subject><subject>Connexin 30</subject><subject>Connexin 43 - metabolism</subject><subject>Connexins - metabolism</subject><subject>Diffusion</subject><subject>Energy metabolism</subject><subject>Epilepsy - physiopathology</subject><subject>Excitatory Postsynaptic Potentials</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gap junctions</subject><subject>Gap Junctions - physiology</subject><subject>Glucose - metabolism</subject><subject>Glutamic Acid - metabolism</subject><subject>Hippocampus - blood supply</subject><subject>Hippocampus - cytology</subject><subject>Hippocampus - physiology</subject><subject>In Vitro Techniques</subject><subject>Lactates</subject><subject>Lactic Acid - metabolism</subject><subject>Life Sciences</subject><subject>Metabolic Networks and Pathways</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Molecular biology</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurons - physiology</subject><subject>Neuroscience</subject><subject>Patch-Clamp Techniques</subject><subject>Pipettes</subject><subject>Proteins</subject><subject>Pyramidal cells</subject><subject>Receptors, AMPA - metabolism</subject><subject>Synaptic Transmission</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqF0s1v0zAYBnALgVgZnDkBFdJAHMr8EX8dq2msSAUO3c6W69jDJY0zOwHtv-etEg3EgZ6i5PnllfPkReglwR8JoeK8uOhb5-FGVJjSR2hGsOYLTTF7jGYYM7FQWPIT9KyUHcaQafYUnRCNudBKztDVsvQ53TbRNvMvvrfb1EQ3_-r7Xyn_KPPNUHob2_kqdl1ydt8B29y3tutBXWfbln0sJab2OXoSbFP8i-l6im4-XV5frBbrb1efL5brhRO86hfcSlrVzglMtKh0RXAtXK0lpywE63hNmdfbmgatOXMyeKW09VLzOmyDVoqdog_j3O-2MV2Oe5vvTbLRrJZrc3iGqWBMMfWTgH0_2i6nu8GX3sBhnW8a2_o0FCMrVinoS4J8918JXQklKnYUMkG5UpQchZQQqYnQRyHRXKjxjG__gbs05BbKhmGMQ4eEAzofkcuplOzDQ0cEm8PGmGljzLQx8Mbraeyw3fv6j59WBMDZBGxxtgnw010sD45irTBRhw95Nbpd6VP-KydSaCEgfzPmwSZjbzPMuNlAyjDhQlKO2W9NTdrw</recordid><startdate>20081205</startdate><enddate>20081205</enddate><creator>Rouach, Nathalie</creator><creator>Koulakoff, Annette</creator><creator>Abudara, Veronica</creator><creator>Willecke, Klaus</creator><creator>Giaume, Christian</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><general>American Association for the Advancement of Science (AAAS)</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-5574-888X</orcidid></search><sort><creationdate>20081205</creationdate><title>Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission</title><author>Rouach, Nathalie ; Koulakoff, Annette ; Abudara, Veronica ; Willecke, Klaus ; Giaume, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c654t-5a724dcc6019649410d6cd97523ffac5d23e9bd2f9953c7fe889ae795dfbf9883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Astrocytes</topic><topic>Astrocytes - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Blood vessels</topic><topic>Cell Membrane Permeability</topic><topic>Cellular biology</topic><topic>Connexin 30</topic><topic>Connexin 43 - metabolism</topic><topic>Connexins - metabolism</topic><topic>Diffusion</topic><topic>Energy metabolism</topic><topic>Epilepsy - physiopathology</topic><topic>Excitatory Postsynaptic Potentials</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gap junctions</topic><topic>Gap Junctions - physiology</topic><topic>Glucose - metabolism</topic><topic>Glutamic Acid - metabolism</topic><topic>Hippocampus - blood supply</topic><topic>Hippocampus - cytology</topic><topic>Hippocampus - physiology</topic><topic>In Vitro Techniques</topic><topic>Lactates</topic><topic>Lactic Acid - metabolism</topic><topic>Life Sciences</topic><topic>Metabolic Networks and Pathways</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Molecular biology</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Neurons - physiology</topic><topic>Neuroscience</topic><topic>Patch-Clamp Techniques</topic><topic>Pipettes</topic><topic>Proteins</topic><topic>Pyramidal cells</topic><topic>Receptors, AMPA - metabolism</topic><topic>Synaptic Transmission</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rouach, Nathalie</creatorcontrib><creatorcontrib>Koulakoff, Annette</creatorcontrib><creatorcontrib>Abudara, Veronica</creatorcontrib><creatorcontrib>Willecke, Klaus</creatorcontrib><creatorcontrib>Giaume, Christian</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rouach, Nathalie</au><au>Koulakoff, Annette</au><au>Abudara, Veronica</au><au>Willecke, Klaus</au><au>Giaume, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2008-12-05</date><risdate>2008</risdate><volume>322</volume><issue>5907</issue><spage>1551</spage><epage>1555</epage><pages>1551-1555</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. 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subjects | Animals Astrocytes Astrocytes - metabolism Biological and medical sciences Blood Glucose - metabolism Blood vessels Cell Membrane Permeability Cellular biology Connexin 30 Connexin 43 - metabolism Connexins - metabolism Diffusion Energy metabolism Epilepsy - physiopathology Excitatory Postsynaptic Potentials Fundamental and applied biological sciences. Psychology Gap junctions Gap Junctions - physiology Glucose - metabolism Glutamic Acid - metabolism Hippocampus - blood supply Hippocampus - cytology Hippocampus - physiology In Vitro Techniques Lactates Lactic Acid - metabolism Life Sciences Metabolic Networks and Pathways Metabolism Mice Mice, Knockout Mice, Transgenic Molecular biology Neurology Neurons Neurons - physiology Neuroscience Patch-Clamp Techniques Pipettes Proteins Pyramidal cells Receptors, AMPA - metabolism Synaptic Transmission Vertebrates: nervous system and sense organs |
title | Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission |
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