TY - JOUR TI - Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery AU - Mei, Feng AU - Lehmann-Horn, Klaus AU - Shen, Yun-An A AU - Rankin, Kelsey A AU - Stebbins, Karin J AU - Lorrain, Daniel S AU - Pekarek, Kara AU - A Sagan, Sharon AU - Xiao, Lan AU - Teuscher, Cory AU - von Büdingen, H-Christian AU - Wess, Jürgen AU - Lawrence, J Josh AU - Green, Ari J AU - Fancy, Stephen PJ AU - Zamvil, Scott S AU - Chan, Jonah R A2 - Nave, Klaus-Armin VL - 5 PY - 2016 DA - 2016/09/27 SP - e18246 C1 - eLife 2016;5:e18246 DO - 10.7554/eLife.18246 UR - https://doi.org/10.7554/eLife.18246 AB - 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. KW - demyelination KW - myelination KW - oligodendrocytes JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -