Siklós L, Engelhardt J I, Alexianu M E, Gurney M E, Siddique T, Appel S H
Department of Neurology, Baylor College of Medicine, Tex 77030, USA.
J Neuropathol Exp Neurol. 1998 Jun;57(6):571-87. doi: 10.1097/00005072-199806000-00005.
Transgenic mice with Cu,Zn superoxide dismutase (SOD-1) mutations provide a unique model to examine altered Ca homeostasis in selectively vulnerable and resistant motoneurons. In degenerating spinal motoneurons of G93 A SOD-1 mice, developing vacuoles were filled with calcium, while calcium was gradually depleted from the cytoplasm and intact mitochondria. In oculomotor neurons, no degenerative changes, vacuolization, or increased calcium were noted. Motor axon terminals of interosseus muscle gradually degenerated and intracellular calcium was depleted. Oculomotor terminals of mutant SOD-1 mice were smaller and exhibited no degenerative changes, but did exhibit unique membrane-enclosed organelles containing calcium. Spinal motoneurons of SOD-1 mice were shown to have fewer calcium binding proteins, such as parvalbumin, compared with oculomotor neurons. These data suggest that the SOD-1 mutation is associated with impaired calcium homeostasis in motoneurons in vivo, with increased likelihood of degeneration associated with higher levels of intracellular calcium and lower to absent levels of calbindin-D28K and/or parvalbumin, and decreased likelihood of degeneration associated with minimally changed calcium and ample calbindin-D28K and/or parvalbumin.
携带铜锌超氧化物歧化酶（SOD-1）突变的转基因小鼠为研究选择性易损和抗性运动神经元中钙稳态的改变提供了一个独特的模型。在G93A SOD-1小鼠退化的脊髓运动神经元中，正在形成的液泡充满了钙，而钙则从细胞质和完整的线粒体中逐渐耗尽。在动眼神经神经元中，未观察到退行性变化、空泡化或钙增加。骨间肌的运动轴突终末逐渐退化，细胞内钙耗尽。突变型SOD-1小鼠的动眼神经终末较小，未表现出退行性变化，但确实表现出含有钙的独特膜包被细胞器。与动眼神经神经元相比，SOD-1小鼠的脊髓运动神经元显示出较少的钙结合蛋白，如小白蛋白。这些数据表明，SOD-1突变与体内运动神经元的钙稳态受损有关，细胞内钙水平较高以及钙结合蛋白-D28K和/或小白蛋白水平较低或缺失时，退化的可能性增加；而钙变化最小以及钙结合蛋白-D28K和/或小白蛋白充足时，退化的可能性降低。
