The 5-hydroxytryptamine 4 Receptor Agonist-induced Actions and Enteric Neurogenesis in the Gut.
The 5-hydroxytryptamine 4 Receptor Agonist-induced Actions and Enteric Neurogenesis in the Gut.
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DOI：
10.5056/jnm.2014.20.1.17
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发表时间：
2014-01
影响因子：
3.4
通讯作者：
Kawahara I
中科院分区：
文献类型：
--
作者：
Takaki M;Goto K;Kawahara I
我们探索了5-羟色胺4受体（5-HT 4 R）激动剂在体内重建肠神经回路的新作用，该回路介导基本的远端肠反射。采用豚鼠和大鼠直肠横断吻合法建立神经回路损伤模型。5-HT 4 R激动剂枸橼酸莫沙必利（MOS）在吻合部位口服和局部应用2周，促进受损神经回路的再生或远端肠反射的恢复。MOS在吻合口肉芽组织中产生神经丝、5-HT 4 R和5-溴-2 '-脱氧尿苷阳性细胞并形成神经网络。可能的神经干细胞标志物在同一时期增加。特异性5-HT_4 R拮抗剂GR_（113808）或SB-207266可抑制MOS的上述作用。肠神经5-HT 4 R的激活促进可能涉及神经干细胞的肠神经回路的重建。我们还成功地形成了密集的肠神经网络的MOS在肠道从小鼠胚胎干细胞分化。GR抑制肠神经网络的形成。MOS可上调5-HT 4 R mRNA的表达，而GR可阻断这种上调作用，提示MOS通过激活5-HT 4 R介导肠神经网络的分化。在小肠中的H-线：Thy 1启动子绿色荧光蛋白（GFP）小鼠，我们获得了清晰的三维成像肠神经元，新产生的口服应用MOS肠横断和吻合后。所有研究结果表明，5-HT 4 R激动剂治疗可能是一种新的治疗方法，用于产生新的肠神经元，以拯救整个肠道中的无神经节疾病。
We explored a novel effect of 5-hydroxytryptamine 4 receptor (5-HT4R) agonists in vivo to reconstruct the enteric neural circuitry that mediates a fundamental distal gut reflex. The neural circuit insult was performed in guinea pigs and rats by rectal transection and anastomosis. A 5-HT4R-agonist, mosapride citrate (MOS) applied orally and locally at the anastomotic site for 2 weeks promoted the regeneration of the impaired neural circuit or the recovery of the distal gut reflex. MOS generated neurofilament-, 5-HT4R- and 5-bromo-2'-deoxyuridine-positive cells and formed neural network in the granulation tissue at the anastomosis. Possible neural stem cell markers increased during the same time period. These novel actions by MOS were inhibited by specific 5-HT4R-antagonist such as GR113808 (GR) or SB-207266. The activation of enteric neural 5-HT4R promotes reconstruction of an enteric neural circuit that involves possibly neural stem cells. We also succeeded in forming dense enteric neural networks by MOS in a gut differentiated from mouse embryonic stem cells. GR abolished the formation of enteric neural networks. MOS up-regulated the expression of mRNA of 5-HT4R, and GR abolished this upregulation, suggesting MOS differentiated enteric neural networks, mediated via activation of 5-HT4R. In the small intestine in H-line: Thy1 promoter green fluorescent protein (GFP) mice, we obtained clear 3-dimensional imaging of enteric neurons that were newly generated by oral application of MOS after gut transection and anastomosis. All findings indicate that treatment with 5-HT4R-agonists could be a novel therapy for generating new enteric neurons to rescue aganglionic disorders in the whole gut.
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影响因子：
3.3
作者：
GERSHON, MD;TAMIR, H
通讯作者：
TAMIR, H
DOI：
10.1073/pnas.93.2.867
发表时间：
1996-01-23
影响因子：
11.1
作者：
Gariepy, CE;Cass, DT;Yanagisawa, M
通讯作者：
Yanagisawa, M
影响因子：
12.6
作者：
Andresen, Viola;Montori, Victor M.;Camilleri, Michael
通讯作者：
Camilleri, Michael
DOI：
10.1152/ajpgi.1998.275.3.g433
发表时间：
1998-09-01
影响因子：
4.5
作者：
Chen, JX;Pan, H;Gershon, MD
通讯作者：
Gershon, MD
影响因子：
2.9
作者：
BAEYENS, R;REYNTJENS, A;VERLINDEN, M
通讯作者：
VERLINDEN, M