| Brain metabolism dictates the polarity of astrocyte control over arterioles. | |
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MedLine Citation:
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PMID: 18971930 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E(2), leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation. |
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Authors:
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Grant R J Gordon; Hyun B Choi; Ravi L Rungta; Graham C R Ellis-Davies; Brian A MacVicar |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-10-29 |
Journal Detail:
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Title: Nature Volume: 456 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-16 Completed Date: 2008-12-30 Revised Date: 2011-06-15 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
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Languages: eng Pagination: 745-9 Citation Subset: IM |
Affiliation:
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Brain Research Centre, Department of Psychiatry, University of British Columbia, British Columbia T2N 2B5, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine
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metabolism,
pharmacology Animals Arterioles / drug effects, metabolism* Astrocytes / metabolism* Brain / blood supply*, metabolism* Dinoprostone / metabolism Glycolysis Lactic Acid / metabolism Male Organic Anion Transporters / metabolism Oxygen / metabolism Pressure Prostaglandin-Endoperoxide Synthases / metabolism Rats Rats, Sprague-Dawley Vasoconstriction / drug effects, physiology* Vasodilation / drug effects, physiology* Vasodilator Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM053395-13/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Organic Anion Transporters; 0/Slco2a1 protein, rat; 0/Vasodilator Agents; 363-24-6/Dinoprostone; 50-21-5/Lactic Acid; 58-61-7/Adenosine; 7782-44-7/Oxygen; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases |
| Comments/Corrections | |
Comment In:
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Nature. 2008 Dec 11;456(7223):715-6
[PMID:
19079043
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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