PDF(Pubmed)
Abstract：
Serotonin (5-hydroxytryptamine, 5HT) homeostasis is essential for many physiological processes in the central nervous system and peripheral tissues. Hyperserotonemia, a measurable sign of 5HT homeostasis disruption, can be caused by 5HT-directed treatment of psychiatric and gastrointestinal diseases. Its impact on the long-term balance and function of 5HT in the peripheral compartment remains unresolved and requires further research due to possible effects on human health. We explored the effects of perinatal 5HT imbalance on the peripheral organs responsible for serotonin metabolism-the jejunum, a synthesis site, and the liver, a catabolism site-in adult rats. Hyperserotonemia was induced by subchronic treatment with serotonin precursor 5-hydroxytryptophan (5HTP) or serotonin degradation inhibitor tranylcypromine (TCP). The jejunum and liver were collected on postnatal day 70 and analyzed histomorphometrically. Relative mRNA levels of 5HT-regulating proteins were determined using qRT-PCR. Compared to controls, 5HTP- and TCP-treated rats had a reduced number of 5HT-producing cells and expression of the 5HT-synthesising enzyme in the jejunum, and an increased expression of 5HT-transporter accompanied by karyomegaly in hepatocytes, with these differences being more pronounced in the TCP-treated animals. Here, we report that perinatal 5HT disbalance induced long-term cellular and molecular changes in organs regulating 5HT-metabolism, which may have a negative impact on 5HT availability and function in the periphery. Our rat model demonstrates a link between the developmental abnormalities of serotonin homeostasis and 5HT-related changes in adult life and may be suitable for exploring the neurobiological substrates of vulnerability to behavioral and metabolic disorders, as well as for modeling the adverse effects of the prenatal exposure to 5HT enhancers in the human population.
摘要：
5-羟色胺（5-羟色胺，5HT）体内平衡对于中枢神经系统和外周组织中的许多生理过程至关重要。高血清素血症,5HT稳态破坏的可测量信号，可引起精神和胃肠道疾病的5HT定向治疗。其对外周隔室中5HT的长期平衡和功能的影响仍未解决，并且由于对人类健康的可能影响而需要进一步研究。我们探讨了围产期5HT失衡对负责5-羟色胺代谢的周围器官-空肠的影响，一个合成位点，还有肝脏,成年大鼠的分解代谢位点。用5-羟色胺前体5-羟色氨酸（5HTP）或5-羟色胺降解抑制剂tranylcypromine（TCP）亚慢性治疗可诱发高血清羟色胺血症。在出生后第70天收集空肠和肝脏，并进行组织形态计量学分析。使用qRT-PCR测定5HT调节蛋白的相对mRNA水平。与对照组相比，5HT和TCP处理的大鼠在空肠中产生5HT的细胞数量和5HT合成酶的表达减少，肝细胞中5HT-转运体的表达增加并伴有核肿大，这些差异在TCP处理的动物中更为明显。这里,我们报道，围产期5HT失衡引起调节5HT代谢的器官的长期细胞和分子变化，这可能会对周边5HT的可用性和功能产生负面影响。我们的大鼠模型证明了5-羟色胺稳态的发育异常与成年生活中5HT相关的变化之间的联系，并且可能适合于探索行为和代谢紊乱易感性的神经生物学底物。以及对人群中产前暴露于5HT增强剂的不利影响进行建模。
