Brain metabolism dictates the polarity of astrocyte control over arterioles.

Abstract:

: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.

journal_name

Nature

journal_title

Nature

authors

Gordon GR,Choi HB,Rungta RL,Ellis-Davies GC,MacVicar BA

doi

10.1038/nature07525

subject

Has Abstract

pub_date

2008-12-11 00:00:00

pages

745-9

issue

7223

eissn

0028-0836

issn

1476-4687

pii

nature07525

journal_volume

456

pub_type

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