Role of GDNF, GFRα1 and GFAP in a Bifidobacterium-Intervention Induced Mouse Model of Intestinal Neuronal Dysplasia

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.

Enteric glia as a player of gut-brain interactions during Parkinson’s disease

“…Among the changes in the microbiome during PD, the variation of the Bifidobacterium, Lactobacillus, and Akkermansia genera stands out-being those recognized genera by the SCFA production (Romano et al, 2021). Studies with the reintroduction of SCFAs as butyrate or propionate in different animal models of PD demonstrate significant improvements in motor and cognitive deficits and IEB permeability (Kakoty et al, 2021;Liu et al, 2022). Bifidobacterium genus especially appears to impose an immune regulation on enteric glia that is variable among bacteria of this genus (Yang Y. et al, 2022).…”

“…Bifidobacterium has also been correlated to improving the IEB by tight junctions modulation-a probiotic-based therapy proposed for PD patients (Tan et al, 2021;Di Vito et al, 2022). Interestingly, Bifidobacterium animalis can regulate GFAP and GDNF, glial proteins associated with the state of the IEB (Liu et al, 2022). In parallel, when treated with distinct Bifidobacterium species, the MPTP animal model of PD improved the CNS oxidative stress condition, protected the gut barrier, and suppressed the glial hyperactivation state (Li et al, 2022).…”