Département de neurosciences, Université de Montréal, Québec, Canada.
Groupe de recherche sur le système nerveux central, Université de Montréal, Québec, Canada.
Elife. 2018 Oct 15;7:e41973. doi: 10.7554/eLife.41973.
Despite being an early event in ALS, it remains unclear whether the denervation of neuromuscular junctions (NMJ) is simply the first manifestation of a globally degenerating motor neuron. Using in vivo imaging of single axons and their NMJs over a three-month period, we identify that single motor-units are dismantled asynchronously in mice. We reveal that weeks prior to complete axonal degeneration, the dismantling of axonal branches is accompanied by contemporaneous new axonal sprouting resulting in synapse formation onto nearby NMJs. Denervation events tend to propagate from the first lost NMJ, consistent with a contribution of neuromuscular factors extrinsic to motor neurons, with distal branches being more susceptible. These results show that NMJ denervation in ALS is a complex and dynamic process of continuous denervation and new innervation rather than a manifestation of sudden global motor neuron degeneration.
尽管神经肌肉接点（NMJ）失神经支配是 ALS 中的早期事件，但 NMJ 失神经支配是否仅仅是广泛退化的运动神经元的最初表现尚不清楚。通过对单个轴突及其 NMJ 进行为期三个月的活体成像，我们发现单个运动神经元在小鼠中异步解体。我们揭示了在完全轴突退化前数周，轴突分支的解体伴随着同时发生的新轴突发芽，导致形成突触并连接到附近的 NMJ。去神经事件往往从第一个丢失的 NMJ 开始传播，这与运动神经元外在的神经肌肉因素有关，远端分支更容易受到影响。这些结果表明，ALS 中的 NMJ 失神经支配是一个复杂和动态的连续去神经和新神经支配过程，而不是突然的全局运动神经元退化的表现。
