CALCIUM SIGNALING ACTIVATION PROCESS OF MICROGLIA CELLS

描述：小胶质细胞是人类主要的完全免疫活性细胞。 在大脑中，它们的功能类似于周围组织中的巨噬细胞。 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，甚至创伤和中风等急性事件都有很强的 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中枢机制 多种细胞功能，包括增殖。然而，牵涉其中的 钙离子及不同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，并由我们的 实验观察，我们假设钙动员在 在小胶质细胞激活中起关键作用。因此，我们建议进行实验， 将：1)确定识别激活的小胶质细胞的标准，评估离子 通道表达水平、细胞因子产生、形态变化和 免疫细胞化学；2)探讨小胶质细胞激活依赖于 钙信号的大小、持续时间和时间模式；3)调查 CRAC通道在小胶质细胞激活中的作用；4)评估 小胶质细胞激活中的ATP门控通道；5)评估相关的作用和 CRAC和ATP门控通道激活小胶质细胞的效果；6)鉴定 涉及钙信号的生理性和病理性小胶质细胞激活物 和7)研究钙信号传导机制的串扰。 各种小胶质细胞激活剂。 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的组合(膜片钳 电生理学、视频显微镜和双波长荧光测定法)。我们会 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补充 研究钙信号转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启发 了解小胶质细胞中的钙信号事件，并可能产生 确定未来治疗干预目标的信息 可归因于小胶质细胞激活的严重中枢神经系统病变。

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.