Department of Neurobiology, Poznan University of Physical Education, Poznań, Poland.
Université de Paris, Centre National de la Recherche Scientifique (CNRS), Saints-Pères Paris Institute for the Neurosciences (SPPIN), Paris, France.
Physiol Rep. 2021 Jan;9(2):e14706. doi: 10.14814/phy2.14706.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of largely unknown pathophysiology, characterized by the progressive loss of motoneurons (MNs). We review data showing that in presymptomatic ALS mice, MNs display reduced intrinsic excitability and impaired level of excitatory inputs. The loss of repetitive firing specifically affects the large MNs innervating fast contracting muscle fibers, which are the most vulnerable MNs in ALS. Interventions that aimed at restoring either the intrinsic excitability or the synaptic excitation result in a decrease of disease markers in MNs and delayed neuromuscular junction denervation. We then focus on trans-spinal direct current stimulation (tsDCS), a noninvasive tool, since it modulates the activity of spinal neurons and networks. Effects of tsDCS depend on the polarity of applied current. Recent work shows that anodal tsDCS induces long-lasting enhancement of MN excitability and synaptic excitation of spinal MNs. Moreover, we show preliminary results indicating that anodal tsDCS enhances the excitatory synaptic inputs to MNs in ALS mice. In conclusion, we suggest that chronic application of anodal tsDCS might be useful as a complementary method in the management of ALS patients.
肌萎缩侧索硬化症（ALS）是一种病因不明的致命神经退行性疾病，其特征是运动神经元（MNs）进行性丧失。我们回顾了一些数据，这些数据表明在症状前 ALS 小鼠中，MNs 表现出内在兴奋性降低和兴奋性输入水平受损。重复放电的丧失特别影响到支配快速收缩肌纤维的大型 MNs，而这些 MNs 是 ALS 中最易受影响的 MNs。旨在恢复内在兴奋性或突触兴奋的干预措施可降低 MNs 中的疾病标志物，并延迟运动神经元-肌肉接头的去神经支配。然后，我们将重点放在经颅直流电刺激（tsDCS）上，这是一种非侵入性工具，因为它可以调节脊髓神经元和网络的活动。tsDCS 的效果取决于施加电流的极性。最近的工作表明，阳极 tsDCS 可诱导 MN 兴奋性的持久增强和脊髓 MN 突触兴奋。此外，我们还展示了初步结果，表明阳极 tsDCS 可增强 ALS 小鼠 MN 的兴奋性突触输入。总之，我们认为慢性应用阳极 tsDCS 可能作为 ALS 患者治疗的辅助方法有用。
