Brain metabolism dictates the polarity of astrocyte control over arterioles.
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.
Gordon
Grant R J
GR
Brain Research Centre, Department of Psychiatry, University of British Columbia, British Columbia T2N 2B5, Canada.
Choi
Hyun B
HB
Rungta
Ravi L
RL
Ellis-Davies
Graham C R
GC
MacVicar
Brian A
BA
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D006019:Glycolysis; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D027361:Organic Anion Transporters / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011312:Pressure; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D027361:Organic Anion Transporters; C503528:Slco2a1 protein, rat; D014665:Vasodilator Agents; D019344:Lactic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D000241:Adenosine; D015232:Dinoprostone; D010100:Oxygen