Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239, USA.
J Neurosci. 2012 Aug 29;32(35):12028-37. doi: 10.1523/JNEUROSCI.0408-12.2012.
Axonal spheroids occur as part of the pathology of a variety of neurologic diseases. Reactive oxygen species (ROS) trigger formation of spheroids, axonal severing, and Ca(2+) overload. The mechanisms by which ROS lead to the spheroid formation at specific axonal sites remain elusive. Here, using adult mouse primary neurons, we investigate the role of Ca(2+), its regulating systems, and cytoskeletal changes in formation of axonal spheroids triggered by ROS. The results reveal that dramatically higher axoplasmic Ca(2+) levels occur at the sites of axonal spheroids than in the rest of the axon. High focal axoplasmic Ca(2+) levels correlate with focal aggregation of the reverse Na(+)/Ca(2+) exchanger 1, voltage-gated N-type Ca(2+) channel α1B subunit, and actin at the sites of spheroids in individual axons. This study provides new insights into the mechanism of a spheroid formation at specific sites along axons undergoing oxidative stress and a basis for new neuroprotective strategies.
轴突球体是多种神经疾病病理的一部分。活性氧（ROS）引发球体形成、轴突切断和 Ca(2+)超载。ROS 导致特定轴突部位形成球体的机制仍不清楚。在这里，我们使用成年小鼠原代神经元研究 ROS 引发的轴突球体形成中 Ca(2+)及其调节系统和细胞骨架变化的作用。结果表明，在轴突球体部位的轴浆 Ca(2+)水平明显高于轴突的其余部分。高焦点轴浆 Ca(2+)水平与焦点聚集在个体轴突中球体部位的反向 Na(+)/Ca(2+)交换器 1、电压门控 N 型 Ca(2+)通道 α1B 亚基和肌动蛋白相关。这项研究为氧化应激下特定部位轴突球体形成的机制以及新的神经保护策略提供了新的见解。
