Abstract
ObjectiveTo investigate the effects of glial cell-derived neurotrophic factor (GDNF), GDNF family receptor alpha 1 (GFRα1), and glial fibrillary acidic protein (GFAP) on colonic motility in a mouse model of intestinal neuronal dysplasia by intervention with Bifidobacterium and to explore the influence of Bifidobacterium on enteric glial cells (EGCs).MethodsWestern blotting and qRT-PCR were employed to detect the expression of GFRα1 and GFAP in colonic tissues of mice with or without Tlx2 mutations, and ELISA was used to detect the expression of GDNF in serum. IHC was used to detect the appearance of the ganglion cells. Subsequently, Tlx2 homozygous mutant (Tlx2−/−) mice were treated with Bifidobacterium. Colonic motility was measured before and after intervention by measuring the glass bead expelling time. The variations in abdominal circumference and GDNF, GFRα1, and GFAP expression were measured. In addition, 16SrRNA gene sequencing was performed to detect the abundance of the intestinal microbiota.ResultsThe mRNA and protein expression of GFRα1 and GFAP was decreased in the colonic tissues of Tlx2−/− mice and GDNF expression was decreased in serum compared with Tlx2+/− and WT mice. After confirming the colonization of Bifidobacterium by 16S rRNA gene sequencing, the expelling time and abdominal distension were ameliorated, and the expression of GFAP, GDNF, and GFRα1 was increased.ConclusionsThe expression of GDNF, GFRα1, and GFAP is associated with colonic motility. The altered expression of EGC-related factors suggested that Bifidobacterium may be involved in the EGC activation process. The amelioration of IND symptoms after intervention with Bifidobacterium prompted the elicitation of adjuvant therapy.
Highlights
Intestinal neuronal dysplasia (IND) is a disorder of the enteric nervous system (ENS) associated with intestinal dysmotility [1]
This study aimed to explore the effects of Glial cell line-derived neurotrophic factor (GDNF), GFRα1, and Glial fibrillary acidic protein (GFAP) on colonic motility and the influence of Bifidobacterium animalis on enteric neuroglial cells (EGCs), and to further clarify the potential pathogenesis of IND
To confirm whether the expressions of GDNF, GFRα1, and GFAP were different among WT, T-Cell Leukemia Homeobox Protein 2 (Tlx2)+/−, and Tlx2−/− mice, the colonic samples and sera of these mice were used for analysis
Summary
Intestinal neuronal dysplasia (IND) is a disorder of the enteric nervous system (ENS) associated with intestinal dysmotility [1]. The pathological features of IND are distinct, and include: hyperplasia of the submucosal nerve plexus, immaturity of ganglia, and hypertrophy of the nerve trunks in clinical cases [2, 3]. The histopathological diagnostic criteria for IND are continuously updated, its etiology and pathogenesis have not been elucidated. Glial cell line-derived neurotrophic factor (GDNF), secreted by enteric neuroglial cells (EGCs), are regarded as one of the most important neurotrophic pathways in the formation of the ENS [5]. Signals through the activation of downstream signaling pathways direct the development of the ENS, including neuroblast migration and axonal outgrowth [6, 7]
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