Effect of Neuroligin1 and Neurexin1 on the Colonic Motility in a Mouse Model of Neuronal Intestinal Dysplasia

Aim. To investigate the expressions of neuroligin1 (NL1) and neurexin1 (NX1) in a mouse model of neuronal intestinal dysplasia (Tlx2-/- mice) and to explore their effects on colonic motility. Methods. Immunohistochemistry staining was employed to explore the histological appearances of NL1, NX1, the presynaptic marker of glutamatergic synapses VGLUT1, and the subunit of NMDA receptors of NR1 in the colon of mice with or without Tlx2 mutation. Western blotting and qRT-PCR were performed to detect their relative expressions in the colon. Colonic motility was measured by a glass bead technique. Then, the Tlx2-/- mice were intervened by Huperzine A. Variations on expressions of NL1, NX1, VGLUT1, and NR1 and variations on colonic motility were measured. Additionally, serum concentrations of Glu were measured by ELISA. Results. Immunohistochemistry staining reveals that NL1, NX1, VGLUT1, and NR1 were mainly concentrated in the myenteric plexus of ENS. Compared to those in WT and Tlx2+/- mice, expressions of NL1 and NX1 in colon of Tlx2-/- mice were upregulated with increased VGLUT1 and NR1 abundances and impaired colonic motility (P<0.05). After intervention, the upregulated expressions of NL1 and NX1 were decreased with a correlated reduce of VGLUT1 and NR1 and a recovery of the impaired colonic motility (P<0.05). Variations of serum concentrations of Glu measured by ELISA were in concordance with the variations of glutamatergic synapses and colonic motility (P<0.05). Conclusion. NL1 and NX1 are closely related to the colonic motility through their effects of targeting the formation of glutamatergic synapses and may be involved in the pathogenesis of NID. The variations of serum Glu seem to be a potential and less painful auxiliary measure for colonic motility and NID.

Congenital Segmental Intestinal Dilatation: A 25-Year Review with Long-Term Follow-up at the Medical University of Innsbruck, Austria

Background and Aim Congenital segmental intestinal dilatation (CSID) is a neonatal condition with unclear etiology and pathogenesis. Typically, the newborn with CSID presents with a limited (circumscribed) bowel dilatation, an abrupt transition between normal and dilated segments, neither intrinsic nor extrinsic perilesional obstruction, and no aganglionosis or neuronal intestinal dysplasia. We aimed to review this disease and the long-term follow-up at the Children's Hospital of the Medical University of Innsbruck, Tyrol, Austria. Study Design Retrospective 25-year review of medical charts, electronic files, and histopathology of neonates with CSID. Results We identified four infants (three girls and one boy) with CSID. The affected areas included duodenum, ileum, ascending colon, and sigmoid colon. Noteworthy, all patients presented with a cardiovascular defect, of which two required multiple cardiac surgical interventions. Three out of the four patients recovered completely. To date, the three infants are alive. Conclusion This is the first report of patients with CSID and cardiovascular defects. The clinical and surgical intervention for CSID also requires a thorough cardiologic evaluation in these patients. CSID remains an enigmatic entity pointing to the need for joint forces in identifying common loci for genetic investigations.

Hirschsprung's disease

Hirschprung's disease 280Neuronal intestinal dysplasia 281Intestinal pseudo-obstruction 281Hirschsprung's disease is the absence of ganglion cells in the myenteric plexus of the most distal bowel. Presentation is with constipation. Incidence is 1 in 5000. Long-segment Hirschsprung's disease is familial, with equal sex incidence. The gene is on chromosome 10. It is associated with Down's syndrome and there is a high frequency of other congenital abnormalities....