Prenatal maternal stress induces visceral hypersensitivity of adult rat offspring through activation of cystathionine-β-synthase signaling in primary sensory neurons.
Prenatal maternal stress induces visceral hypersensitivity of adult rat offspring through activation of cystathionine-β-synthase signaling in primary sensory neurons.
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产前母体应激通过激活初级感觉神经元中的胱硫醚-β-合酶信号诱导成年大鼠后代的内脏超敏反应。
DOI：
10.1177/1744806918777406
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发表时间：
2018-01
期刊：
影响因子：
3.3
通讯作者：
Xu GY
中科院分区：
文献类型：
--
作者：
Wang HJ;Xu X;Xie RH;Rui YY;Zhang PA;Zhu XJ;Xu GY
肠易激综合征是一种病因不明的疾病，其特征是与排便改变相关的广泛的慢性腹痛。越来越多的证据表明，妊娠期的应激源可能会对后代的组织结构和功能产生长期影响，这可能会导致胃肠道疾病。本研究的目的是确定产前母亲的压力是否是影响胃肠敏感性的一个不利因素，并探讨可能的机制，产前母亲的压力诱导的内脏高敏感性的成年后代。通过从妊娠第7天到分娩暴露于异型间歇性应激，在妊娠Sprague-Dawley大鼠中诱导产前母体应激。出生前母亲的压力显着增加内脏反应的结直肠扩张的成年后代从6周龄至10周龄。产前母体应激还增强了神经元的兴奋性，包括静息膜电位的去极化，基强度的减少，以及由2倍和3倍基强度电流刺激结肠特异性背根神经节神经元诱发的动作电位数目的增加。妊娠期母体应激显著增强T13-L2胸腰段背根神经节中胱硫醚-β-合成酶和Nav 1. 7的蛋白和mRNA表达。腹腔注射氨基氧乙酸（一种胱硫醚-β-合酶抑制剂）以剂量依赖性方式减轻产前母体应激诱导的内脏高敏感性。连续7天给予氨基氧乙酸逆转了结肠特异性背根神经节神经元的过度兴奋，并显着降低Nav1.7的表达。这些结果表明，妊娠期间多种心理物理应激源的存在与后代的内脏高敏感性相关，这可能是由胱硫醚-β-合成酶和Nav1.7表达的上调介导的。产前母亲的压力可能是肠易激综合征的一个重要因素，胱硫醚-β-合酶可能是治疗肠易激综合征患者慢性内脏高敏感性的一个潜在靶点。
Irritable bowel syndrome is a disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that stressors presented during gestational periods could have long-term effects on the offspring’s tissue structure and function, which may predispose to gastrointestinal diseases. The aim of the present study is to determine whether prenatal maternal stressis a adverse factor affecting gastrointestinal sensitivity and to investigate possible mechanisms underlying prenatal maternal stress-induced visceral hypersensitivity in adult offspring. Prenatal maternal stress was induced in pregnant Sprague–Dawley rats by exposure to heterotypic intermitent stress from gestational day 7 to delivery. Prenatal maternal stress significantly increased visceromotor response to colorectal distention in adult offspring from the age of 6 weeks to 10 weeks. Prenatal maternal stress also enhanced neuronal excitability including depolarization of resting membrane potentials, reduction in rheobase, and an increase in the number of action potentials evoked by 2× and 3× rheobase current stimultion of colon-specific dorsal root ganglion neurons. Prenatal maternal stress remarkably enhanced expression of cystathionine-β-synthase and Nav1.7 in T13-L2 thoracolumbar dorsal root ganglions both at protein and mRNA levels. Intraperitoneal injection of aminooxyacetic acid, an inhibitor of cystathionine-β-synthase, attenuated prenatal maternal stress-induced visceral hypersensitivity in a dose-dependent manner. A consecutive seven-day administration of aminooxyacetic acid reversed the hyperexcitability of colon-specific dorsal root ganglion neurons and markedly reduced Nav1.7 expression. These results indicate that the presence of multiple psychophysical stressors during pregnancy is associated with visceral hypersensitivity in offspring, which is likely mediated by an upregualtion of cystathionine-β-synthase and Nav1.7 expression. Prenatal maternal stress might be a significant contributor to irritable bowel syndrome, and cystathionine-β-synthase might be a potential target for treatment for chronic visceral hypersensitivity in patients with irritable bowel syndrome.
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影响因子：
7.5
作者：
Sayem, Abu Sadat Md;Giribabu, Nelli;Salleh, Naguib
通讯作者：
Salleh, Naguib
影响因子：
6.6
作者：
Kabil, Omer;Vitvitsky, Victor;Banerjee, Ruma
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DOI：
10.1097/med.0b013e3283405921
发表时间：
2010-12
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Entringer S;Buss C;Wadhwa PD
通讯作者：
Wadhwa PD
影响因子：
3.5
作者：
Campaniello, M. A.;Harrington, A. M.;Hughes, P. A.
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Hughes, P. A.
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DOI：
10.1152/ajpgi.00466.2012
发表时间：
2013-05-01
影响因子：
4.5
作者：
Qu, Ruobing;Tao, Jingde;Xu, Guang-Yin
通讯作者：
Xu, Guang-Yin