Document Detail


Brain metabolism dictates the polarity of astrocyte control over arterioles.
MedLine Citation:
PMID:  18971930     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Grant R J Gordon; Hyun B Choi; Ravi L Rungta; Graham C R Ellis-Davies; Brian A MacVicar
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-29
Journal Detail:
Title:  Nature     Volume:  456     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2008-12-30     Revised Date:  2011-06-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  745-9     Citation Subset:  IM    
Affiliation:
Brain Research Centre, Department of Psychiatry, University of British Columbia, British Columbia T2N 2B5, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adenosine / 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:
R01 GM053395-13/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
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:
Nature. 2008 Dec 11;456(7223):715-6   [PMID:  19079043 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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