Alzheimer's amyloid β-peptide enhances ATP/gap junction-mediated calcium-wave propagation in astrocytes
Alzheimer's amyloid β-peptide enhances ATP/gap junction-mediated calcium-wave propagation in astrocytes
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DOI：
10.1385/nmm:3:3:173
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发表时间：
2003-01-01
影响因子：
3.5
通讯作者：
Mattson, MP
中科院分区：
文献类型：
--
作者：
Haughey, NJ;Mattson, MP
阿尔茨海默氏病 (AD) 涉及淀粉样 P 肽 (Abeta) 的进行性细胞外沉积，Abeta 是一种自我聚集的 40-42 个氨基酸蛋白，可损害神经元，导致神经元功能障碍和死亡。对神经元的研究表明，Abeta 会扰乱细胞钙稳态，从而增加对诱导钙流入或从内部储存释放的激动剂的钙反应。最近在星形胶质细胞中发现的细胞间钙波表明星形胶质细胞在神经系统的长距离信息传递中发挥着有趣的作用。我们现在报道 Abeta 改变培养的大鼠皮质星形胶质细胞中的钙波信号。将星形胶质细胞暴露于 AbetaI-42 会导致诱发钙波的幅度和速度增加，并增加波传播的距离。苏拉明减少了未经处理的星形胶质细胞中的波传播，并消除了 Abeta 对钙波振幅和速度的增强作用，表明波传播需要细胞外 ATP。用间隙连接解偶联剂处理星形胶质细胞并没有显着降低对照培养物中钙波的幅度、速度或距离，但完全消除了 Abeta 对三个波参数中每一个的影响。这些发现揭示了 Abeta 对星形胶质细胞中细胞间钙信号传播的新作用，并且还表明星形胶质细胞钙信号传导改变在 AD 发病机制中的作用。
Alzheimer's disease (AD) involves the progressive extracellular deposition of amyloid P-peptide (Abeta), a self-aggregating 40-42 amino acid protein that can damage neurons resulting in their dysfunction and death. Studies of neurons have shown that Abeta perturbs cellular-calcium homeostasis so that calcium responses to agonists that induce calcium influx or release from internal stores are increased. The recent discovery of intercellular calcium waves in astrocytes suggests intriguing roles for astrocytes in the long-range transfer of information in the nervous system. We now report that Abeta alters calcium-wave signaling in cultured rat cortical astrocytes. Exposure of astrocytes to AbetaI-42 resulted in an increase in the amplitude and velocity of evoked calcium waves, and increased the distance the waves traveled. Suramin decreased wave propagation in untreated astrocytes and abrogated the enhancing effect of Abeta on calcium-wave amplitude and velocity, indicating a requirement for extracellular ATP in wave propagation. Treatment of astrocytes with an uncoupler of gap junctions did not significantly reduce the amplitude, velocity, or distance of calcium waves in control cultures, but completely abolished the effects of Abeta on each of the three wave parameters. These findings reveal a novel action of Abeta on the propagation of intercellular calcium signals in astrocytes, and also suggests a role for altered astrocyte calcium-signaling in the pathogenesis of AD.