Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles.
Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles.
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作者：
活跃的神经元通过扩张附近的小动脉和毛细血管来增加能量供应。这种神经血管耦合是BOLD功能成像信号的基础，但其机制存在争议。通常，神经元释放谷氨酸激活星形胶质细胞上的代谢性谷氨酸受体（mGluR5），从内部储存中释放Ca2+，激活磷脂酶A2并产生血管扩张性花生四烯酸衍生物。然而，成人星形胶质细胞缺乏mGluR5，敲除IP3受体释放Ca2+不影响神经血管偶联。我们现在表明，缓冲的星形胶质细胞Ca2+抑制神经元引起的毛细血管扩张，星形胶质细胞[Ca2+]i不是通过从储存释放而是通过atp门控通道进入而升高，Ca2+通过磷脂酶D2和二酰基甘油激酶而不是磷脂酶A2产生花生四烯酸。相反，小动脉的扩张依赖于NMDA受体的激活和中间神经元Ca2+依赖性NO的产生。这些结果表明，不同的信号级联在毛细血管和小动脉水平上调节脑血流。
Active neurons increase their energy supply by dilating nearby arterioles and capillaries. This neurovascular coupling underlies BOLD functional imaging signals, but its mechanism is controversial. Canonically, neurons release glutamate to activate metabotropic glutamate receptors (mGluR5) on astrocytes, evoking Ca2+ release from internal stores, activating phospholipase A2 and generating vasodilatory arachidonic acid derivatives. However, adult astrocytes lack mGluR5, and knock-out of the IP3 receptors that release Ca2+ from stores does not affect neurovascular coupling. We now show that buffering astrocyte Ca2+ inhibits neuronally-evoked capillary dilation, that astrocyte [Ca2+]i is raised not by release from stores but by entry through ATP-gated channels, and that Ca2+ generates arachidonic acid via phospholipase D2 and diacylglycerol kinase rather than phospholipase A2. In contrast, dilation of arterioles depends on NMDA receptor activation and Ca2+-dependent NO generation by interneurons. These results reveal that different signalling cascades regulate cerebral blood flow at the capillary and arteriole levels.
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DOI：
10.1523/jneurosci.3285-12.2013
发表时间：
2013-05-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Nizar K;Uhlirova H;Tian P;Saisan PA;Cheng Q;Reznichenko L;Weldy KL;Steed TC;Sridhar VB;MacDonald CL;Cui J;Gratiy SL;Sakadzić S;Boas DA;Beka TI;Einevoll GT;Chen J;Masliah E;Dale AM;Silva GA;Devor A
通讯作者：
Devor A
影响因子：
16.2
作者：
Haustein MD;Kracun S;Lu XH;Shih T;Jackson-Weaver O;Tong X;Xu J;Yang XW;O'Dell TJ;Marvin JS;Ellisman MH;Bushong EA;Looger LL;Khakh BS
通讯作者：
Khakh BS
影响因子：
64.8
作者：
Mulligan, SJ;MacVicar, BA
通讯作者：
MacVicar, BA
影响因子：
8.3
作者：
Alkayed, NJ;Narayanan, J;Harder, DR
通讯作者：
Harder, DR
影响因子：
5.3
作者：
Metea, MR;Newman, EA
通讯作者：
Newman, EA