Istanbul Medipol Üniversity, School of Medicine, Department of Physiology, Istanbul, Turkey.
Neuropathol Appl Neurobiol. 2013 Jun;39(4):362-76. doi: 10.1111/j.1365-2990.2012.01295.x.
In many neurodegenerative diseases and following traumas, dying back degeneration is a common phenomenon that aggravates the pathology and may eventually lead to death of the affected neurone. We aimed to investigate the mechanism of dying back degeneration with an in vitro axonal injury model.
We cultured adult mouse dorsal root ganglion neurones and with a precise laser beam, cut the axons they extended. Preparations were imaged continuously and images were analysed to describe and quantify ensuing events. Potential contributions of calpains and caspases to the degeneration were explored using specific inhibitors and immunohistochemistry. In vivo implications of the results were sought in nerve sections after sciatic nerve cut.
The proximal part of the transected axons went under basically two types of dying back degeneration, fragmentation and retraction. In fragmentation the cytoplasm became condensed and with concomitant axial collapse the axon disintegrated into small pieces. In retraction, the severed axon was pulled back to the soma in an organized manner. We demonstrated that fragmentation was associated with a high risk of cell death, while survival rate with retraction was as high as those of uninjured neurones. Regeneration of transected axon was more likely after retraction than following fragmentation. Activities of caspase-3 and calpains but not of caspase-6 were found linked with retraction and regeneration but not with the fragmentation.
This study describes two quite distinct types of dying back degeneration that lead an injured neurone to quite different fates.
在许多神经退行性疾病和创伤后，退行性变是一种常见的现象，它会加重病变，最终可能导致受影响的神经元死亡。我们旨在通过体外轴突损伤模型研究退行性变的机制。
我们培养成年小鼠背根神经节神经元，并用精确的激光束切断它们伸出的轴突。连续对制备物进行成像，并对图像进行分析，以描述和量化随后发生的事件。使用特异性抑制剂和免疫组织化学方法探讨钙蛋白酶和半胱天冬酶对退行性变的潜在贡献。在坐骨神经切断后的神经切片中，研究了体内结果的意义。
被切断的轴突的近端部分基本上经历了两种类型的退行性变，即碎裂和回缩。在碎裂中，细胞质变得浓缩，伴随着轴向崩溃，轴突分解成小块。在回缩中，被切断的轴突以有序的方式被拉回到胞体。我们证明，碎裂与细胞死亡的高风险相关，而回缩的存活率与未受伤的神经元一样高。回缩后轴突的再生比碎裂后更有可能。发现半胱天冬酶-3 和钙蛋白酶的活性与回缩和再生有关，但与碎裂无关。
本研究描述了两种截然不同的退行性变类型，它们导致受伤的神经元走向截然不同的命运。
