Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Duke University Medical Center Box 2644, Durham, North Carolina, 27710, USA.
Sci Rep. 2020 Jun 2;10(1):8967. doi: 10.1038/s41598-020-65824-1.
Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by deleterious mutations in the DMD gene which encodes the dystrophin protein. Skeletal muscle weakness and eventual muscle degradation due to loss of dystrophin are well-documented pathological hallmarks of DMD. In contrast, the neuropathology of this disease remains understudied despite the emerging evidence of neurological abnormalities induced by dystrophin loss. Using quantitative morphological analysis of nerve sections, we characterize axonopathies in the phrenic and hypoglossal (XII) nerves of mdx mice. We observe dysfunction in these nerves - which innervate the diaphragm and genioglossus respectively - that we propose contributes to respiratory failure, the most common cause of death in DMD. These observations highlight the importance in the further characterization of the neuropathology of DMD. Additionally, these observations underscore the necessity in correcting both the nervous system pathology in addition to skeletal muscle deficits to ameliorate this disease.
杜氏肌营养不良症（DMD）是一种致命的神经肌肉疾病，由 DMD 基因的有害突变引起，该基因编码肌营养不良蛋白。由于肌营养不良蛋白的缺失导致骨骼肌无力和最终肌肉退化是 DMD 的明确病理特征。相比之下，尽管有肌营养不良蛋白缺失导致神经异常的新证据，但这种疾病的神经病理学仍然研究不足。我们使用神经切片的定量形态分析，对 mdx 小鼠的膈神经和舌下神经（XII）的轴突病变进行了特征描述。我们观察到这些神经的功能障碍 - 它们分别支配膈肌和颏舌肌 - 我们认为这导致了呼吸衰竭，这是 DMD 最常见的死亡原因。这些观察结果强调了进一步描述 DMD 神经病理学的重要性。此外，这些观察结果强调了除了纠正骨骼肌缺陷之外，还必须纠正神经系统病理学，以改善这种疾病。
