Abstract：
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by motor neuron death and distal axonopathy. Despite its clinical severity and profound impact in the patients and their families, many questions about its pathogenesis remain still unclear, including the role of Schwann cells and axon-glial signaling in disease progression. Upon axonal injury, upregulation of JUN transcription factor promotes Schwann cell reprogramming into a repair phenotype that favors axon regrowth and neuronal survival. To study the potential role of repair Schwann cells on motoneuron survival in amyotrophic lateral sclerosis, we generated a mouse line that over-expresses JUN in the Schwann cells of the SOD1G93A mutant, a mouse model of this disease. Then, we explored disease progression by evaluating survival, motor performance and histology of peripheral nerves and spinal cord of these mice. We found that Schwann cell JUN overexpression does not prevent axon degeneration neither motor neuron death in the SOD1G93A mice. Instead, it induces a partial demyelination of medium and large size axons, worsening motor performance and resulting in more aggressive disease phenotype.
摘要：
肌萎缩侧索硬化症是一种破坏性的神经退行性疾病，其特征是运动神经元死亡和远端轴突病变。尽管其临床严重程度和对患者及其家人的深远影响，关于其发病机制的许多问题仍不清楚，包括雪旺氏细胞和轴突-神经胶质信号在疾病进展中的作用。在轴突损伤时，JUN转录因子的上调促进雪旺氏细胞重编程为有利于轴突再生和神经元存活的修复表型。研究雪旺氏细胞修复对肌萎缩侧索硬化症运动神经元存活的潜在作用。我们产生了一个在SOD1G93A突变体的施万细胞中过表达JUN的小鼠系，这种疾病的小鼠模型。然后，我们通过评估生存率来探索疾病进展，这些小鼠的周围神经和脊髓的运动表现和组织学。我们发现，在SOD1G93A小鼠中，雪旺氏细胞JUN过表达既不能防止轴突变性，也不能防止运动神经元死亡。相反，它诱导中型和大型轴突的部分脱髓鞘，运动表现恶化，导致疾病表型更具侵略性。
