| Abstract No.: | C-G3199 |
| Country: | Canada |
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| Title: | BRAIN METABOLIC STATE DICTATES THE POLARITY OF ASTROCYTE CONTROL OVER THE CEREBROVASCULATURE
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| Authors/Affiliations: | 1 Grant R. J. Gordon*; 1 Hyun Beom Choi; 1 Brian A. MacVicar;
1 Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
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| Content: | Enhanced neuronal activity and metabolic demands of brain tissue increase cerebral blood flow (CBF). Ca2+ changes in astrocytes are critical in coupling activity to regional alterations in CBF by eliciting vasoconstriction or vasodilation of adjacent arterioles. However it is not known if the metabolic state of the brain itself influences the polarity of astrocyte control over the cerebrovascular. Using two-photon Ca2+ imaging and uncaging, intrinsic nicotinamide adenine dinucleotide (NADH) imaging of single cells as a measure of brain redox state, as well as assays for the release of lactate and prostaglandin E2 (PGE2) we show that the ability of astrocytes to induce vasodilations over vasoconstrictions critically relies on the glycolytic state of the tissue which is altered by oxygen (O2) availability. When PO2 is lowered, but remains within a physiological range, astrocyte-mediated constrictions are converted to vasodilations. This effect relies on enhanced glycolysis in astrocytes and the subsequent release of lactate which facilitates PGE2 efflux through prostaglandin transporter via lactate exchange. These results provide a mechanism for how astrocytes change their type of influence over CBF when PO2 levels are altered by the state of brain activation. |
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