Macroglossia and less advanced dystrophic change in the tongue muscle of the Duchenne muscular dystrophy rat

Abstract

Background Duchenne muscular dystrophy (DMD) is an X-linked muscle disease caused by a complete lack of dystrophin, which stabilizes the plasma membrane of myofibers. The orofacial function is affected in an advanced stage of DMD and this often leads to an eating disorder such as dysphagia. Dysphagia is caused by multiple etiologies including decreased mastication and swallowing. Therefore, preventing the functional declines of mastication and swallowing in DMD is important to improve the patient’s quality of life. In the present study, using a rat model of DMD we generated previously, we performed analyses on the masseter and tongue muscles, both are required for proper eating function. Methods Age-related changes of the masseter and tongue muscle of DMD rats were analyzed morphometrically, histologically, and immunohistochemically. Also, transcription of cellular senescent markers, and utrophin (Utrn), a functional analog of dystrophin, was examined. Results The masseter muscle of DMD rats showed progressive dystrophic changes as observed in their hindlimb muscle, accompanied by increased transcription of p16 and p19. On the other hand, the tongue of DMD rats showed macroglossia due to hypertrophy of myofibers with less dystrophic changes. Proliferative activity was preserved in the satellite cells from the tongue muscle but was perturbed severely in those from the masseter muscle. While Utrn transcription was increased in the masseter muscle of DMD rats compared to WT rats, probably due to a compensatory mechanism, its level in the tongue muscle was comparable between WT and DMD rats and was similar to that in the masseter muscle of DMD rats. Conclusions Muscular dystrophy is less advanced in the tongue muscle compared to the masseter muscle in the DMD rat.

Biomarkers for Duchenne muscular dystrophy progression: impact of age in the mdx tongue spared muscle

“…In DMD rats, the tongue showed hypertrophy of myofibers with less advanced dystrophic changes until 9 months old compared to masseter. This resistance against degeneration might be related to a higher transcription level of utrophin in tongue of wild-type and DMD rats compared to masseter of wild-type rats [ 37 ]. Increased expression of utrophin in the skeletal muscles of mdx mice results in a functional improvement in muscle function [ 38 – 40 ].…”