Wang Dongming, Gao Ni, Zhou Tingting, Zhang Qiangye, Wang Jian, Li Aiwu
Department of Pediatric Surgery, Qilu Hospital, Shandong University, China.
Gastroenterol Res Pract. 2020 Jan 4;2020:9818652. doi: 10.1155/2020/9818652. eCollection 2020.
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.
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.
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 ( < 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 ( < 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 ( < 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 (.
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.
研究神经元肠道发育异常小鼠模型（Tlx2小鼠）中神经连接蛋白1（NL1）和神经纤毛蛋白1（NX1）的表达情况，并探讨它们对结肠运动的影响。
采用免疫组织化学染色法观察野生型及Tlx2突变型小鼠结肠中NL1、NX1、谷氨酸能突触前标记物VGLUT1以及N-甲基-D-天冬氨酸受体亚基NR1的组织学表现。运用蛋白质免疫印迹法和实时定量聚合酶链反应检测它们在结肠中的相对表达量。通过玻璃珠技术测量结肠运动。随后，用石杉碱甲对Tlx2小鼠进行干预。检测NL1、NX1、VGLUT1和NR1表达的变化以及结肠运动的变化。此外，采用酶联免疫吸附测定法检测血清谷氨酸（Glu）浓度。
免疫组织化学染色显示，NL1、NX1、VGLUT1和NR1主要集中在肠神经系统的肌间神经丛。与野生型和Tlx2小鼠相比，Tlx2小鼠结肠中NL1和NX1的表达上调，VGLUT1和NR1丰度增加，结肠运动受损（P<0.05）。干预后，NL1和NX1的上调表达降低，VGLUT1和NR1相应减少，受损的结肠运动恢复（P<0.05）。干预后，NL1和NX1的上调表达降低，VGLUT1和NR1相应减少，受损的结肠运动恢复（P<0.05）。干预后，NL1和NX1的上调表达降低，VGLUT1和NR1相应减少，受损的结肠运动恢复（P<0.05）。
NL1和NX1通过靶向谷氨酸能突触的形成对结肠运动有密切影响，可能参与神经元肠道发育异常的发病机制。血清Glu的变化似乎是一种潜在的、痛苦较小的评估结肠运动和神经元肠道发育异常的辅助手段。
