CALCIUM SIGNALING ACTIVATION PROCESS OF MICROGLIA CELLS

描述：小胶质细胞是主要的完全免疫活性细胞， 它们在脑中发挥与外周组织中的巨噬细胞类似的功能。 越来越明显的是，大多数慢性神经退行性疾病，如 阿尔茨海默氏症，甚至急性事件，如创伤和中风， 涉及小胶质细胞的免疫成分。 其他免疫活性细胞使用钙信号作为核心机制， 许多细胞功能，包括增殖。然而，参与 钙离子和不同的钙信号机制在小胶质细胞中的作用 激活在很大程度上是未知的。在文献中指出，并得到我们的支持 实验观察，我们假设钙动员发挥了重要作用， 在小胶质细胞激活中起关键作用。因此，我们提出的实验， 将：1）确定识别激活小胶质细胞的标准，评估离子 通道表达水平、细胞因子产生、形态学变化和 免疫细胞化学; 2）探索小胶质细胞活化对细胞周期的依赖性。 钙信号的幅度、持续时间和时间模式; 3）研究 CRAC通道在小胶质细胞活化中的作用; 4）评估CRAC通道在小胶质细胞活化中的作用。 ATP门控通道在小胶质细胞活化中的作用; 5）评估ATP门控通道在小胶质细胞活化中的相对作用， CRAC和ATP门控通道在激活小胶质细胞中的功效; 6）鉴定 涉及钙信号传导的生理和病理性小胶质细胞激活剂 和7）研究由以下物质引发的钙信号传导机制的串扰： 各种小胶质细胞激活剂。 该实验室研究这些问题的方法是在单细胞水平上 并采用生物物理技术（膜片钳）的组合 电生理学、视频显微术和双波长荧光测定法）。我们将 评估生理参数，如离子通量，膜电位，和 细胞内钙水平。这些技术得到了以下技术的补充 研究钙信号传导的免疫荧光和药理学工具 在小胶质细胞中。对上述问题的回答将有助于 了解小胶质细胞中的钙信号传导事件， 确定未来治疗干预目标的信息， 可归因于小胶质细胞活化的严重CNS病理。

DESCRIPTION: Microglia cells are the major fully immunocompetent cells of the brain, where they serve similar functions as macrophages in peripheral tissues. It is becoming apparent that most chronic neurodegenerative diseases, such as Alzheimer's, and even acute events such as trauma and stroke have strong immunological components involving microglia cells. Other immunocompetent cells use calcium signaling as central mechanism for numerous cellular functions, including proliferation. However, the involvement of calcium and the role of different calcium signaling mechanisms in microglia activation is largely unknown. Indicated in the literature and supported by our experimental observations, we hypothesize that calcium mobilization plays a pivotal role in microglia activation. We therefore propose experiments that will: 1) Identify criteria do discern activated microglia, evaluating ion channel expression levels, cytokine production, morphological changes and immunocytochemistry; 2) Explore the dependence of microglia activation on the magnitude, duration and temporal patterns of calcium signals; 3) Investigate the role of CRAC channels in microglia activation; 4) Assess the role of ATP-gated channels in microglia activation; 5) Assess the relative roles and efficacies of CRAC and ATP-gated channels in activating microglia; 6) Identify physiological and pathological microglia activators involving calcium signaling and 7) Investigate the cross-talk of calcium signaling mechanisms initiated by various microglia activators. The laboratory's approach to study these questions is at the single-cell level and employs a combination of biophysical techniques (patch-clamp electrophysiology, video microscopy, and dual-wavelength fluorometry). We will assess physiological parameters such as ionic fluxes, membrane potential, and intracellular calcium levels. These techniques are complemented by immunofluorescence and pharmacological tools to investigate calcium signaling in microglia cells. Answers to the questions above will enlighten the understanding of the calcium signaling events in microglia cells and may yield information to identify future targets for therapeutic intervention in the serious CNS pathologies that are attributable to microglia activation.