Photothrombosis ischemia stimulates a sustained astrocytic Ca2+ signaling in vivo.
Photothrombosis ischemia stimulates a sustained astrocytic Ca2+ signaling in vivo.
复制标题
光栓塞性缺血刺激体内持续的星形细胞Ca2+信号传导。
DOI：
10.1002/glia.20804
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发表时间：
2009-05
期刊：
影响因子：
6.2
通讯作者：
Haydon, Philip G.
中科院分区：
文献类型：
--
作者：
Ding, Shinghua;Wang, Tiannan;Cui, Wenju;Haydon, Philip G.
虽然有关于脑缺血对神经元功能的后果的重要信息，但对中枢神经系统（CNS）中主要的神经胶质细胞类型星形胶质细胞的功能反应知之甚少。在这项研究中，我们询问局灶性缺血是否会影响星形胶质细胞Ca 2+信号传导，这是这种细胞类型兴奋性的特征形式。在绿色光照射循环虎红引发的光血栓诱导缺血急性期，使用双光子（2-P）显微镜对皮质星形胶质细胞进行体内Ca 2+成像。尽管胡须诱发电位在光血栓形成后几分钟内降低了90%以上，但缺血核心中的星形胶质细胞在几个小时内保持结构完整。在体内钙离子成像显示，在缺血20分钟内，星形胶质细胞中的瞬时钙离子信号增加。这些Ca 2+信号是同步的，并在神经胶质网络中以波的形式传播。药理学研究表明，这些Ca ~（2+）信号依赖于代谢型谷氨酸受体5（mGluR 5）和代谢型γ-氨基丁酸受体（GABABR）的激活，而不依赖于P_2嘌呤受体或A_1腺苷受体。用BAPTA选择性抑制星形胶质细胞中的Ca 2+可显着减少梗死体积，这表明增强的星形胶质细胞Ca 2+信号可能通过Ca 2+依赖性的胶质谷氨酸释放而导致神经元损伤。由于星形胶质细胞与神经元和血管系统密切沟通，提供多种功能，缺血诱导的星形胶质细胞Ca 2+信号的增加可能代表了这些细胞与神经元沟通或提供反馈调节血管系统的最初尝试。
While there is significant information concerning the consequences of cerebral ischemia on neuronal function, relatively little is known about functional responses of astrocytes, the predominant glial-cell type in the central nervous system (CNS). In this study, we asked whether focal ischemia would impact astrocytic Ca2+ signaling, a characteristic form of excitability in this cell type. In vivo Ca2+ imaging of cortical astrocytes was performed using two-photon (2-P) microscopy during the acute phase of photothrombosis-induced ischemia initiated by green light illumination of circulating Rose Bengal. Although whisker evoked potentials were reduced by over 90% within minutes of photothrombosis, astrocytes in the ischemic core remained structurally intact for a few hours. In vivo Ca2+ imaging showed that an increase in transient Ca2+ signals in astrocytes within 20 min of ischemia. These Ca2+ signals were synchronized and propagated as waves amongst the glial network. Pharmacological manipulations demonstrated that these Ca2+ signals were dependent on activation of metabotropic glutamate receptor 5 (mGluR5) and metabotropic γ-aminobutyric acid receptor (GABABR) but not by P2 purinergic receptor or A1 adenosine receptor. Selective inhibition of Ca2+ in astrocytes with BAPTA significantly reduced the infarct volume, demonstrating that the enhanced astrocytic Ca2+ signal contributes to neuronal damage presumably through Ca2+-dependent release of glial glutamate. Since astrocytes offer multiple functions in close communication with neurons and vasculature, the ischemia-induced increase in astrocytic Ca2+ signaling may represent an initial attempt for these cells to communicate with neurons or provide feed back regulation to the vasculature.
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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：
6.2
作者：
Gunnarson, Eli;Zelenina, Marina;Aperia, Anita
通讯作者：
Aperia, Anita
影响因子：
48
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
5.3
作者：
Bushong, EA;Martone, ME;Ellisman, MH
通讯作者：
Ellisman, MH
影响因子：
82.9
作者：
Mattiasson, G;Shamloo, M;Wieloch, T
通讯作者：
Wieloch, T