Respiratory failure is the leading cause of death in Duchenne muscular dystrophy (DMD), a devastating neuromuscular disorder caused by the loss of dystrophin. Although classically thought to be disease that only affects muscles, DMD also results in neurological impairments in approximately one-third of patients. Respiratory muscle pathology in DMD is well-described; however, pathology in the respiratory control centers, particularly within the medulla remains unclear. The medulla contains rhythm-generating neurons and circuits essential for breathing. The goal of this study is to identify the cellular and molecular changes within the medulla in the preclinical mdx mouse model of DMD using single-nucleus RNA sequencing (snRNA-seq). 12mo mdx mice and wild-type (WT) controls (n=3 per genotype) medullas were harvested and analyzed using snRNA-seq to generate a high-resolution atlas of cell type–specific transcriptomic alterations. In mdx mice, oligodendrocytes had dysregulation of mitochondrial pathways which suggests compromised myelination and reduced axonal metabolic support. Further, astrocytes and microglia had alterations in molecular pathways that affect GTPase-mediated signal transduction, gliogenesis, neuronal development, and synaptic function. In addition, there was an increased number of microglia in the mdx mice suggesting an inflammatory response in the brainstem. These findings indicate that in the medulla of mdx mice, there is glial and neuroimmune dysfunction, which implies that central mechanisms could also contribute to respiratory instability. In conclusion, this study illustrates the impact of dystrophin deficiency on the central nervous system (CNS) and highlights the importance of using novel therapies to target CNS as well as muscle dysfunction. Funding: NHLBI R01HL171282 (MKE) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Biswas et al. (2026) studied this question.