Synaptic vesicle morphology and recycling are altered in myenteric neurons of mice lacking dystrophin (mdx mice)

Abstract

Several dystrophin isoforms are known. The full-length isoform is present in striated and smooth muscles and neurons and its lack causes Duchenne Muscular Dystrophy, a progressive myopathy accompanied by mild cognitive deficits and gastrointestinal dismotility. An ultrastructural study was undertaken in the colon of mice lacking full-length dystrophin and maintaining shorter isoforms (mdx mice) to ascertain whether myenteric neurons have an altered morphology. Results showed a significant increase in the size of synaptic vesicle and in the number of recycling vesicles. An enlargement of endoplasmic reticulum cisternae in a subpopulation of neurons was also seen. Immunohistochemistry confirmed that the shorter isoforms were expressed in mdx mice myenteric neurons. These findings indicate the presence of a neuropathy at the myenteric plexus which might justify the defective neuronal control of gastrointestinal motility reported for these animals and which might be correlated with full-length dystrophin loss, since the shorter isoforms are present.

Discrepancies between c‐Kit positive and Ano1 positive ICC‐SMP in the W/Wv and wild‐type mouse colon; relationships with motor patterns and calcium transients

“…The opposite can also be found: no changes in c‐Kit immunohistochemistry but presence of profound ICC cellular ultrastructural changes, observed in a mouse intestine model of Trichinella spiralis inflammation . The same change was also found in mdx mice, an animal model lacking in full‐length dystrophin and used to study Duchenne muscular dystrophy, in which a normal c‐Kit positive network was present but electron microscopy showed marked ultrastructural injury to the ICC . Furthermore, in esophageal atresia of neonates and in the gastroschisis model of fetal rats, there is ultrastructural evidence of ICC precursors or immature ICC but they are c‐Kit negative.…”

Morphological Characterization of the Myenteric Plexus of the Ileum and Distal colon of Dogs Affected by Muscular Dystrophy

“…According to Mulè et al (), the motility of the colon, which may be responsible for constipation in patients with DMD, has yet to be studied, and constipation has been associated with weakness of the abdominal muscles. Additionally, an ultrastructural study of the colon from mice ( mdx mice) demonstrated altered morphology of the myenteric neurons (Vannucchi et al, ).…”

“…According to Mulè et al (2010), the motility of the colon, which may be responsible for constipation in patients with DMD, has yet to be studied, and constipation has been associated with weakness of the abdominal muscles. Additionally, an ultrastructural study of the colon from mice (mdx mice) demonstrated altered morphology of the myenteric neurons (Vannucchi et al, 2003). The enteric nervous system (ENS) is located in the GIT from the esophagus to the external anal sphincter, including the gallbladder, the cystic duct, the common bile duct, and the pancreas.…”

Steroid therapy is associated with decreased numbers of dendritic cells and fibroblasts, and increased numbers of satellite cells, in the dystrophic skeletal muscle

“…The DGC serves as an anchor for the contractile proteins organised in the myofilaments 1. A disruption of the DGC results in a disease process known collectively as muscular dystrophies.…”

“…DMD is the most common and devastating childhood X-linked disorder that can result in early loss of ambulation between the ages of 7 and 13 years. Also, DMD may be associated with subsequent death in the teens and twenties 1. The beneficial therapeutic roles of steroids in muscular dystrophies is supported by the fact that targeted immunosuppression in dystrophic mice can delay the progression of the muscle damage.…”