Astrocyte inositol triphosphate receptor type 2 and cytosolic phospholipase A2 alpha regulate arteriole responses in mouse neocortical brain slices.
Astrocyte inositol triphosphate receptor type 2 and cytosolic phospholipase A2 alpha regulate arteriole responses in mouse neocortical brain slices.
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DOI：
10.1371/journal.pone.0042194
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sapirstein A
中科院分区：
文献类型：
--
作者：
He L;Linden DJ;Sapirstein A
脑血管系统的功能性充血使局部血流与脑的代谢需求相匹配。神经血管控制的一个当前模型认为，由神经元释放的谷氨酸激活星形胶质细胞上的I组代谢型谷氨酸受体（mGluR），导致产生可扩散的信使，其用于调节脑小动脉周围的平滑肌细胞。小鼠急性脑片是一种可以用光学显微镜精确测量脑内微动脉直径变化的实验系统。大脑切片的刺激触发特定的细胞反应，这些反应可以与小动脉直径的变化相关联。在这里，我们使用肌醇三磷酸受体2型（IP 3R 2）和胞浆磷脂酶A2 α（cPLA 2 α）缺陷小鼠，以确定星形胶质细胞mGluR激活耦合IP 3R 2介导的Ca 2+释放和随后的cPLA 2 α激活是否是小动脉调节所必需的。我们测量了星形胶质细胞胞浆游离Ca 2+和小动脉直径的变化，在急性新皮质小鼠脑切片保持在95%或20%O2的mGluR激动剂或电场刺激。星形胶质细胞Ca 2+和小动脉对mGluR激活的反应在IP 3R 2 − /−切片中不存在。星形胶质细胞对mGluR激活的Ca 2+反应未因cPLA 2 α缺失而改变，但小动脉对mGluR激动剂或电刺激的反应被消融。小动脉直径的变化（扩张/收缩）的效价依赖于刺激和O2浓度。神经元衍生的NO和I组mGluRs的激活是对电刺激的反应所必需的。这些结果表明，星形胶质细胞中的mGluR/IP 3R 2/cPLA 2 α信号级联需要抑制神经元谷氨酸释放到小动脉反应中。
Functional hyperemia of the cerebral vascular system matches regional blood flow to the metabolic demands of the brain. One current model of neurovascular control holds that glutamate released by neurons activates group I metabotropic glutamate receptors (mGluRs) on astrocytes, resulting in the production of diffusible messengers that act to regulate smooth muscle cells surrounding cerebral arterioles. The acute mouse brain slice is an experimental system in which changes in arteriole diameter can precisely measured with light microscopy. Stimulation of the brain slice triggers specific cellular responses that can be correlated to changes in arteriole diameter. Here we used inositol trisphosphate receptor type 2 (IP3R2) and cytosolic phospholipase A2 alpha (cPLA2α) deficient mice to determine if astrocyte mGluR activation coupled to IP3R2-mediated Ca2+ release and subsequent cPLA2α activation is required for arteriole regulation. We measured changes in astrocyte cytosolic free Ca2+ and arteriole diameters in response to mGluR agonist or electrical field stimulation in acute neocortical mouse brain slices maintained in 95% or 20% O2. Astrocyte Ca2+ and arteriole responses to mGluR activation were absent in IP3R2− /− slices. Astrocyte Ca2+ responses to mGluR activation were unchanged by deletion of cPLA2α but arteriole responses to either mGluR agonist or electrical stimulation were ablated. The valence of changes in arteriole diameter (dilation/constriction) was dependent upon both stimulus and O2 concentration. Neuron-derived NO and activation of the group I mGluRs are required for responses to electrical stimulation. These findings indicate that an mGluR/IP3R2/cPLA2α signaling cascade in astrocytes is required to transduce neuronal glutamate release into arteriole responses.
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影响因子：
8.3
作者：
Alkayed, NJ;Narayanan, J;Harder, DR
通讯作者：
Harder, DR
影响因子：
3.5
作者：
Balboa, MA;Varela-Nieto, I;Dennis, EA
通讯作者：
Dennis, EA
影响因子：
8.3
作者：
AlonsoGalicia, M;Drummond, HA;Roman, RJ
通讯作者：
Roman, RJ
DOI：
10.1016/s1388-1981(99)00164-x
发表时间：
2000-01-17
影响因子：
4.8
作者：
Abramovitz, M;Adam, M;Metters, KM
通讯作者：
Metters, KM
DOI：
10.1046/j.1365-201x.2000.00707.x
发表时间：
2000-04-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Harder, DR;Roman, RJ;Gebremedhin, D
通讯作者：
Gebremedhin, D