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

Role of GDNF, GFRα1 and GFAP in a Bifidobacterium-Intervention Induced Mouse Model of Intestinal Neuronal Dysplasia.
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GDNF、GFRα1 和 GFAP 在双歧杆菌干预诱导小鼠肠神经元发育不良模型中的作用

DOI:
10.3389/fped.2021.795678
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发表时间:
2021
影响因子:
2.6
通讯作者:
Li A
Li A
中科院分区:
医学3区
文献类型:
--
作者:
Liu W;Zhou T;Tian J;Yu X;Ren C;Cao Z;Hou P;Zhang Q;Li A

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目的:通过双歧杆菌干预,观察胶质细胞源性神经营养因子及其家族受体α1和胶质纤维酸性蛋白对肠神经发育不良小鼠结肠动力的影响,探讨双歧杆菌对肠神经胶质细胞的影响。采用免疫印迹和定量逆转录聚合酶链式反应检测T1x2基因突变前后小鼠结肠组织中胶质细胞源性神经营养因子受体α1和胶质纤维酸性蛋白的表达,用ELISA法检测血清中胶质细胞源性神经营养因子的表达。免疫组织化学方法检测神经节细胞的形态。随后,用双歧杆菌对T1x2纯合子突变(Tlx2−/−)小鼠进行处理。通过测量玻璃微珠排出时间来测量干预前后的结肠动力。观察腹围变化及胶质细胞源性神经营养因子、胶质细胞生长因子受体α1和胶质纤维酸性蛋白的表达。此外,还进行了16SrRNA基因测序,以检测肠道微生物区系的丰度。与Tlx2+/α和WT小鼠相比,−/−组小鼠结肠组织中GFRGFF1和GFAPmRNA和蛋白的表达降低,血清中GDNFmRNA和蛋白的表达降低。16SRRNA基因测序证实双歧杆菌定植后,排出时间和腹胀明显改善,胶质纤维酸性蛋白、胶质细胞源性神经营养因子和胶质细胞生长因子受体α-1的表达增加。胶质细胞源性神经营养因子、胶质细胞生长因子受体α-1和胶质纤维酸性蛋白的表达与结肠动力密切相关。EGC相关因子表达的改变提示双歧杆菌可能参与了EGC的激活过程。双歧杆菌干预后IND症状的改善促使辅助治疗的启发。
To 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). Western 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. The 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. The 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.
DOI: 10.1055/s-2008-1063549
发表时间: 1993-08-01
影响因子: 1.8
作者:
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发表时间: 2007-08-01
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