Axonal injury alters the extracellular glial environment of the axon initial segment and allows substantial mitochondrial influx into axon initial segment
Axonal injury alters the extracellular glial environment of the axon initial segment and allows substantial mitochondrial influx into axon initial segment
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轴突损伤改变了轴突初始段的细胞外神经胶质环境，并允许大量线粒体流入轴突初始段
DOI：
10.1002/cne.25212
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发表时间：
2021
期刊：
影响因子：
2.5
通讯作者：
Kiyama H
中科院分区：
文献类型：
--
作者：
Tamada H;Kiryu-Seo S;Sawada S;Kiyama H
轴突初始段（AIS）在结构和功能上与轴突其他区域不同，但脑损伤后AIS环境的变化尚未得到很好的表征。在这项研究中，我们检查了舌下神经损伤后AIS细胞外和细胞内的变化。在健康对照中很少观察到AIS的小胶质细胞粘附，而在轴突损伤模型中，AIS的小胶质细胞粘附很明显。关于AIS内形态学，我们主要关注线粒体，因为线粒体流入受损轴突似乎对轴突再生至关重要。为了可视化受损轴突中的线粒体，我们使用了atf3:BAC转基因小鼠，其线粒体被标记为GFP以响应神经损伤。这些小鼠在神经损伤后的AIS中明显显示线粒体定位。为了精确地证实光镜观察结果，我们使用聚焦离子束/扫描电子显微镜（FIB/SEM）进行了三维超微结构分析。虽然健康AIS没有被小胶质细胞包围，但损伤后观察到小胶质细胞紧密粘连，粘连过程较厚。FIB/SEM同时可以观察到AIS的线粒体定位。在未损伤神经元的AIS中，很少观察到线粒体，而线粒体则大量定位于细胞体、轴突丘和轴突。有趣的是，在损伤的AIS中，在整个AIS中观察到大量线粒体。综上所述，轴突损伤改变了AIS周围的细胞外胶质环境和AIS细胞内线粒体定位。这些变化可能是轴突损伤后受损神经元再生的关键反应。
The axon initial segment (AIS) is structurally and functionally distinct from other regions of the axon, yet alterations in the milieu of the AIS after brain injury have not been well characterized. In this study, we have examined extracellular and intracellular changes in the AIS after hypoglossal nerve injury. Microglial adhesions to the AIS were rarely observed in healthy controls, whereas microglial adhesions to the AIS became apparent in the axonal injury model. Regarding intra‐AIS morphology, we focused on mitochondria because mitochondrial flow into the injured axon appears critical for axonal regeneration. To visualize mitochondria specifically in injured axons, we usedAtf3:BAC transgenic mice whose mitochondria were labeled with GFP in response to nerve injury. These mice clearly showed mitochondrial localization in the AIS after nerve injury. To precisely confirm the light microscopic observations, we performed three‐dimensional ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM). Although the healthy AIS was not surrounded by microglia, tight microglial adhesions with thick processes adhering to the AIS were observed after injury. FIB/SEM simultaneously allowed the observation of mitochondrial localization in the AIS. In the AIS of non‐injured neurons, few mitochondria were observed, whereas mitochondria were abundantly localized in the cell body, axon hillock, and axon. Intriguingly, in the injured AIS, numerous mitochondria were observed throughout the AIS. Taken together, axonal injury changes the extracellular glial environment surrounding the AIS and intracellular mitochondrial localization in the AIS. These changes would be crucial responses, perhaps for injured neurons to regenerate after axonal injury.
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