Serotonin Effectors Expressed during Palatogenesis: An Immunohistochemical Study
Serotonin Effectors Expressed during Palatogenesis: An Immunohistochemical Study
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发表时间：
2018
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通讯作者：
Hirata;Imura;Sugahara;Natsume;H. Nakamura;Y. Kondo
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作者：
Hirata;Imura;Sugahara;Natsume;H. Nakamura;Y. Kondo
5-羟色胺转运蛋白（Serotonin transporter，SERT）是通过去除细胞外5-HT来协调5-羟色胺（5-hydroxytryptamine，5-HT）信号传导的最关键的调节剂之一。早期研究表明，5-HT通过与5-HT受体或SERT相互作用来调节颅面形态发生。为了确定5-HT和SERT在腭发育中的特征，我们用化学方法检测了它们在小鼠次级腭形成过程中的定位。我们还检测了5-HT的主要代谢酶单胺氧化酶（MAO）和5-HT的合成酶色氨酸羟化酶（TPH）的免疫定位，以阐明它们与5-HT在腭发育中的关系。免疫组化显示，在垂直位置的腭架中，5-HT在腭间充质中弥漫性定位，而SERT、MAO和TPH免疫反应性较弱。当腭架水平时，在腭架外上皮层细胞中观察到类似的5-HT、SERT、MAO和TPH免疫反应性。此外，5-HT，SERT，单胺氧化酶，和TPH的免疫反应中检测到的中间上皮缝（MES）的融合腭架，并与腭形成的进展，这些免疫反应随后观察到在基底和中间层的腭上皮。这些发现表明，通过SERT的Escherichia coli能调节参与腭发育，特别是在腭上皮的发育。我们的研究结果表明，5-羟色胺代谢的改变增加了先天性颅面畸形的风险，如在怀孕期间暴露于选择性5-羟色胺再摄取抑制剂（SSRIs）的妇女的孩子中的唇腭裂
Serotonin transporter (SERT) is one of the most critical regulators of the orchestration of serotonin (5-hydroxytryptamine; 5-HT) signaling through removal of extracellular 5-HT. Early studies have shown that 5-HT regulates craniofacial morphogenesis through interaction with 5-HT receptors or SERT. To determine the characteristics of 5-HT and SERT in palate development, we examined their localization immunohistochemically during secondary palate formation in mice. We also examined the immunolocalization of monoamine oxidase (MAO), a major metabolic enzyme of 5-HT, and tryptophan hydroxylase (TPH), a synthetic enzyme of 5-HT, to clarify their relationship with 5-HT in palatogenesis. Immunohistochemically, in the palatal shelves in the vertical position, diffuse localization of 5-HT was observed in the palatal mesenchyme, whereas SERT, MAO, and TPH immune reactivities were weak. When the palatal shelves were oriented horizontally, similar immune reactivities of 5-HT, SERT, MAO, and TPH were observed in the cells of the outer epithelial layer of the palatal shelf. In addition, 5-HT, SERT, MAO, and TPH immunoreactivities were detected in the medial epithelial seam (MES) of fused palatal shelves, and with the progression of palate formation, these immunoreactivities were subsequently observed in the basal and middle layers of the palatal epithelium. These findings suggest that serotonergic regulation via SERT is involved in palatogenesis, particularly in the development of the palatal epithelium. Our findings imply that altered 5-HT metabolism increases the risk of congenital craniofacial anomalies, such as clefting, in the children of women who are exposed to selective serotonin reuptake inhibitors (SSRIs) during pregnancy