Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), UNC, Friuli, 2434 - 5016, Córdoba, Argentina.
Universidad Nacional de Córdoba, Córdoba, Argentina.
Sci Rep. 2018 Feb 14;8(1):3007. doi: 10.1038/s41598-018-21232-0.
Axonal degeneration occurs in the developing nervous system for the appropriate establishment of mature circuits, and is also a hallmark of diverse neurodegenerative diseases. Despite recent interest in the field, little is known about the changes (and possible role) of the cytoskeleton during axonal degeneration. We studied the actin cytoskeleton in an in vitro model of developmental pruning induced by trophic factor withdrawal (TFW). We found that F-actin decrease and growth cone collapse (GCC) occur early after TFW; however, treatments that prevent axonal fragmentation failed to prevent GCC, suggesting independent pathways. Using super-resolution (STED) microscopy we found that the axonal actin/spectrin membrane-associated periodic skeleton (MPS) abundance and organization drop shortly after deprivation, remaining low until fragmentation. Fragmented axons lack MPS (while maintaining microtubules) and acute pharmacological treatments that stabilize actin filaments prevent MPS loss and protect from axonal fragmentation, suggesting that MPS destruction is required for axon fragmentation to proceed.
轴突退化发生在发育中的神经系统中，以适当建立成熟的回路，也是多种神经退行性疾病的标志。尽管最近对该领域产生了兴趣，但对轴突退化过程中细胞骨架的变化（和可能的作用）知之甚少。我们在体外研究了营养因子撤出（TFW）诱导的发育修剪模型中的肌动蛋白细胞骨架。我们发现，TFW 后早期 F-actin 减少和生长锥塌陷（GCC）发生；然而，防止轴突断裂的处理并不能防止 GCC，表明存在独立的途径。使用超分辨率（STED）显微镜，我们发现轴突肌动蛋白/血影蛋白膜相关周期性骨架（MPS）的丰度和组织在剥夺后不久下降，直到碎片化时仍保持较低水平。碎片化的轴突缺乏 MPS（同时保持微管），而稳定肌动蛋白丝的急性药理处理可防止 MPS 丢失并防止轴突碎片化，表明 MPS 的破坏是轴突碎片化进行所必需的。
