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

Dongming Wang,Jian Wang,Tingting Zhou,Ni Gao,Aiwu Li,Qiangye Zhang

doi:10.1155/2020/9818652

Dongming Wang, Jian Wang + Show 4 more

Open Access

https://doi.org/10.1155/2020/9818652

Copy DOI

Abstract

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). 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). 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 (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.

Highlights

Neuronal intestinal dysplasia (NID) is a clinical condition that resembles Hirschsprung’s disease (HSCR) and is clinically characterized by seriously impaired colonic motility, such as severe constipation or intestinal obstruction [1, 2]
Pathological innervation patterns have been described in the colon of patients with NID, it remains controversial as to whether there is a causal relationship between histological findings and its seriously impaired colonic motility
The wild-type allele was shown as a 568 bp fragment, and the mutant allele was shown as a 395 bp fragment

Summary

Introduction

Neuronal intestinal dysplasia (NID) is a clinical condition that resembles Hirschsprung’s disease (HSCR) and is clinically characterized by seriously impaired colonic motility, such as severe constipation or intestinal obstruction [1, 2]. Different from HSCR in histologically observation, absence of ganglion cells in the myenteric plexus, patients with NID show hyperplasia of the submucous and myenteric plexus with increase in AChE-positive nerve fibers [3]. Pathological innervation patterns have been described in the colon of patients with NID, it remains controversial as to whether there is a causal relationship between histological findings and its seriously impaired colonic motility. Neurexins represent a family of presynaptic neuronal cell adhesion proteins and form transsynaptic complexes with neuroligins, the most well-known postsynaptic ligand of neurexins, by protein domains or heparan sulfate (HS) [5, 6]. Interactions between neurexins and neuroligins orchestrate the events of formation and stabilization of both

Methods

Results

Conclusion