Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprung's disease.
Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprung's disease.
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DOI：
10.1111/nmo.12083
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发表时间：
2013-03
影响因子：
3.5
通讯作者：
Gosain A
中科院分区：
文献类型：
--
作者：
Zaitoun I;Erickson CS;Barlow AJ;Klein TR;Heneghan AF;Pierre JF;Epstein ML;Gosain A
先天性巨结肠症是一种先天性疾病，其中肠神经节，形成神经嵴细胞（NCC），是缺乏从终端肠。运动障碍和便秘是手术干预后持续存在的HSCR的常见特征。这种持续性表明，手术后保留的结肠部分不能支持正常的肠功能。为了阐明这种情况下的缺陷，我们利用HSCR的小鼠模型。使用具有NCC特异性Ednrb缺失的小鼠来测量神经节中的神经元密度和神经递质表达。与het动物相比，在位于P21 Ednrb缺失小鼠的无神经节区近端的部位，神经元密度显著降低，神经递质的表达改变。结肠区域的神经节更小，更孤立，而神经元细胞体的大小增加。表达神经元型一氧化氮合酶（nNOS）和血管活性肠肽（VIP）的神经元的百分比显着增加在Ednrb空。相反，胆碱乙酰转移酶（ChAT）表达的神经元的百分比下降，而P物质是不变的两种基因型之间。这些变化仅限于结肠，在回肠中未检测到。我们证明了神经元密度的变化和Ednrb基因敲除小鼠无神经节细胞区域近端结肠中神经递质表达平衡的改变。神经元密度的降低和nNOS和ChAT表达的互补变化可能是HSCR中运动障碍的原因。
Hirschsprung’s disease (HSCR) is a congenital condition in which enteric ganglia, formed from neural crest cells (NCC), are absent from the terminal bowel. Dysmotility and constipation are common features of HSCR that persist following surgical intervention. This persistence suggests that the portion of the colon that remains post-operatively is not able to support normal bowel function. To elucidate the defects that underlie this condition, we utilized a murine model of HSCR. Mice with NCC specific deletion of Ednrb, were used to measure the neuronal density and neurotransmitter expression in ganglia. At the site located proximal to the aganglionic region of P21 Ednrb null mice, the neuronal density is significantly decreased and the expression of neurotransmitters is altered compared to het animals. The ganglia in this colonic region are smaller and more isolated while the size of neuronal cell bodies is increased. The percentage of neurons expressing neuronal nitric oxide synthase (nNOS) and vasoactive intestinal peptide (VIP) is significantly increased in Ednrb nulls. Conversely, the percentage of choline acetyltransferase (ChAT) expressing neurons is decreased, while Substance P is unchanged between the two genotypes. These changes are limited to the colon and are not detected in the ileum. We demonstrate changes in neuronal density and alterations in the balance of expression of neurotransmitters in the colon proximal to the aganglionic region in Ednrb null mice. The reduced neuronal density and complementary changes in nNOS and ChAT expression may account for the dysmotility seen in HSCR.
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影响因子：
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作者：
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DOI：
10.1152/ajpgi.00558.2007
发表时间：
2008-04-01
影响因子：
4.5
作者：
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