Brain metabolism dictates the polarity of astrocyte control over arterioles.
Brain metabolism dictates the polarity of astrocyte control over arterioles.
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DOI：
10.1038/nature07525
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发表时间：
2008-12-11
期刊：
影响因子：
64.8
通讯作者：
MacVicar BA
中科院分区：
文献类型：
--
作者：
Gordon GR;Choi HB;Rungta RL;Ellis-Davies GC;MacVicar BA
星形胶质细胞中的钙信号通过引起邻近小动脉的血管收缩或血管舒张将脑活动的变化与脑血流量（CBF）的局部改变偶联。然而，这些不同的星形胶质细胞影响如何在具有动态代谢要求的细胞环境中提供脑血管张力的适当变化的机制仍不清楚。CBF的调节最近已被证明与动物和人类中的乳酸/丙酮酸比率紧密耦合，从而与NADH/NAD+比率紧密耦合。我们测试了代谢变化对星形胶质细胞调节脑血管直径的影响，通过操纵随大脑活动动态变化的组织氧合。使用双光子Ca 2+成像和uncaging以及内在的烟酰胺腺嘌呤二核苷酸（NADH）成像的单细胞作为氧化还原状态的措施，我们表明，星形胶质细胞诱导血管舒张的能力，血管收缩严重依赖于组织的代谢状态。当O2可用性降低而星形胶质细胞[Ca 2 +]i升高时，星形胶质细胞糖酵解和乳酸盐释放最大化。细胞外乳酸通过阻碍其转运蛋白介导的摄取而有助于前列腺素E2（PGE 2）的积累，随后引起血管舒张。这些数据揭示了代谢底物在调节CBF中的作用，并提供了在不同的脑激活状态下星形胶质细胞对脑血管直径的差异控制机制。
Calcium signaling in astrocytes couples changes in brain activity to regional alterations in cerebral blood flow (CBF) by eliciting vasoconstriction or vasodilation of adjacent arterioles. However, the mechanism for how these disparate astrocyte influences provide appropriate changes in cerebral vascular tone within a cellular environment that has dynamic metabolic requirements remains unclear. The regulation of CBF has recently been shown to be tightly coupled to the lactate/pyruvate ratio and thus the NADH/NAD+ ratio in animals and humans. We tested the impact of metabolic changes on the regulation of cerebral blood vessel diameter by astrocytes, by manipulating tissue oxygenation which changes dynamically with brain activity. Using two-photon Ca2+ imaging and uncaging as well as intrinsic nicotinamide adenine dinucleotide (NADH) imaging of single cells as a measure of redox state, we show that the ability of astrocytes to induce vasodilations over vasoconstrictions critically relies on the metabolic state of the tissue. When O2 availability is lowered and astrocyte [Ca2+]i is elevated, astrocyte glycolysis and lactate release are maximized. Extracellular lactate contributes to prostaglandin E2 (PGE2) accumulation by hindering its transporter-mediated uptake, subsequently causing vasodilation. These data reveal the role of metabolic substrates in regulating CBF and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation.
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影响因子：
2.5
作者：
D'Agostino, Dominic P.;Putnam, Robert W.;Dean, Jay B.
通讯作者：
Dean, Jay B.
DOI：
10.1073/pnas.94.26.14826
发表时间：
1997-12-23
影响因子：
11.1
作者：
Malonek, D;Dirnagl, U;Grinvald, A
通讯作者：
Grinvald, A
DOI：
10.1073/pnas.95.26.15741
发表时间：
1998-12-22
影响因子：
11.1
作者：
Kleinfeld, D;Mitra, PP;Denk, W
通讯作者：
Denk, W
影响因子：
5.3
作者：
Chaigneau, Emmanuelle;Tiret, Pascale;Charpak, Serge
通讯作者：
Charpak, Serge
影响因子：
5.3
作者：
Metea, MR;Newman, EA
通讯作者：
Newman, EA