McLarnon James G, Choi Hyun B, Lue Lih-Fen, Walker Douglas G, Kim Seung U
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
J Neurosci Res. 2005 Aug 1;81(3):426-35. doi: 10.1002/jnr.20487.
Calcium-sensitive fluorescence microscopy has been used to study Ca2+-dependent signal transduction pathways in microglia obtained from Alzheimer's disease (AD) patients and non-demented (ND) individuals. Data were obtained from nine AD cases and seven ND individuals and included basal levels of intracellular Ca2+ [Ca2+]i, peak amplitudes (Delta[Ca2+]i) and time courses of adenosine triphosphate (ATP) responses and amplitudes of an initial transient response and a subsequent second component of Ca2+ influx through store-operated channels (SOC) induced by platelet-activating factor (PAF). Overall, AD microglia were characterized by significantly higher (20%) basal Ca2+ [Ca2+]i relative to ND cells. The Delta[Ca2+]i of ATP and initial phase of PAF responses, which reflect rapid depletion of Ca2+ from endoplasmic reticulum stores, were reduced by respective values of 63% and 59% in AD cells relative to amplitudes recorded from ND microglia. Additionally, AD microglia showed diminished amplitudes (reduction of 61%) of SOC-mediated Ca2+ entry induced by PAF and prolonged time courses (increase of 60%) of ATP responses with respect to ND microglia. We have generally replicated these results with exposure of human fetal microglia to beta amyloid (5 microM Abeta1-42 applied for 24 hr). Overall, these data indicate significant abnormalities are present in Ca2+-mediated signal transduction in microglia isolated from AD patients.
钙敏荧光显微镜已被用于研究从阿尔茨海默病（AD）患者和非痴呆（ND）个体获取的小胶质细胞中钙依赖信号转导途径。数据来自9例AD病例和7名ND个体，包括细胞内钙（[Ca2+]i）的基础水平、三磷酸腺苷（ATP）反应的峰值幅度（Δ[Ca2+]i）和时间进程，以及由血小板活化因子（PAF）诱导的通过储存-操作性钙通道（SOC）的钙内流初始瞬态反应和随后第二成分的幅度。总体而言，AD小胶质细胞的特征是相对于ND细胞，基础钙[Ca2+]i显著更高（20%）。与从ND小胶质细胞记录的幅度相比，AD细胞中反映内质网储存中钙快速消耗的ATP的Δ[Ca2+]i和PAF反应的初始阶段分别降低了63%和59%。此外，与ND小胶质细胞相比，AD小胶质细胞显示PAF诱导的SOC介导的钙内流幅度减小（降低61%），ATP反应的时间进程延长（增加60%）。我们通过将人胎儿小胶质细胞暴露于β淀粉样蛋白（应用5 microM Abeta1-42 24小时）总体上重复了这些结果。总体而言，这些数据表明从AD患者分离的小胶质细胞中钙介导的信号转导存在显著异常。
