Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery
Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery
复制标题
炎症脱髓鞘过程中加速髓鞘再生可防止轴突损失并改善功能恢复
DOI：
10.7554/elife.18246
复制
发表时间：
2016-09-27
期刊：
影响因子：
7.7
通讯作者：
Chan, Jonah R.
中科院分区：
文献类型：
--
作者：
Mei, Feng;Lehmann-Horn, Klaus;Chan, Jonah R.
MS中的脱髓鞘破坏神经信号并导致轴突变性。虽然髓鞘再生有望恢复失去的功能，但仍不清楚髓鞘再生是否会防止轴突丢失。在实验性自身免疫性脑脊髓炎（EAE）小鼠模型中，炎性脱髓鞘伴随着显著的神经元损失，并且在该模型中髓鞘再生的证据由于持续的炎症、变性和可能的髓鞘再生而复杂化。要证明髓鞘再生的功能意义，就必须选择性地改变髓鞘再生相对于炎症和变性的时间。我们通过直接谱系分析证明了EAE诱导后髓鞘再生加速，并假设新形成的髓鞘在炎症高峰时保持稳定，部分原因是未成熟髓鞘中缺乏MOG表达。M1毒蕈碱受体是少突胶质细胞分化和髓鞘形成的一种有效负调节因子，少突胶质细胞特异性基因消融可加速髓鞘再生，防止轴突丢失并改善功能恢复。总之，我们的研究结果表明，加速髓鞘再生支持轴突的完整性和神经元功能后，炎性脱髓鞘。DOI：http://dx.doi.org/10.7554/eLife.18246.001网站
Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination. DOI: http://dx.doi.org/10.7554/eLife.18246.001