Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome
Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome
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DOI：
10.1152/ajpgi.00400.2006
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发表时间：
2007-03-01
影响因子：
4.5
通讯作者：
Sung, Joseph J. Y.
中科院分区：
文献类型：
--
作者：
Ren, Tian-Hua;Wu, Justin;Sung, Joseph J. Y.
早期生活压力已被认为是肠易激综合征（IBS）的一个危险因素。在IBS动物模型中，我们研究了新生儿母亲分离对内脏运动反应和脑-肠轴上c-fos、5-HT及其受体/转运体表达的影响。在出生后2-21天，雄性新生大鼠被随机分配到每天3小时的母亲分离（MS）或不处理（NH）。结肠直肠球囊扩张（CRD）用于评估腹部戒断反射作为内脏疼痛的替代标志物。取中脑中缝背核、腰骶索和结肠远端组织进行c-fos和5-HT半定量分析。RT-PCR分析5-HT表达、5-HT3受体及5-HT转运体的表达情况。MS大鼠疼痛阈值明显低于NH大鼠。CRD对MS大鼠的腹部戒断反射评分显著高于40,60和80mmhg的扩张压。在MS大鼠中，CRD后腰骶脊髓背角c-fos样免疫反应核数量明显增加。MS大鼠脊髓中5-HT含量显著升高。在结肠中，CRD前MS组和NH组5-HT阳性细胞数和5-HT含量具有可比性。crd后仅MS大鼠5-HT含量显著升高。MS和NH大鼠5-HT3受体和5-HT转运体的蛋白和mRNA表达水平相似。新生儿母分离应激使大鼠在模拟肠易激综合征的结肠中容易产生夸张的神经化学反应和内脏痛觉过敏。
Early life stress has been implicated as a risk factor for irritable bowel syndrome (IBS). We studied the effect of neonatal maternal separation on the visceromotor response and the expression of c-fos, 5-HT, and its receptors/transporters along the brain-gut axis in an animal model of IBS. Male neonatal Sprague-Dawley rats were randomly assigned to a 3-h daily maternal separation (MS) or nonhandling (NH) on postnatal days 2-21. Colorectal balloon distention (CRD) was performed for assessment of abdominal withdrawal reflex as a surrogate marker of visceral pain. Tissues from dorsal raphe nucleus in midbrain, lumbar-sacral cord, and distal colon were harvested for semi-quantitative analysis of c-fos and 5-HT. The expression of 5-HT expression, 5-HT3 receptors, and 5-HT transporter were analyzed by RT-PCR. Pain threshold was significantly lower in MS than NH rats. The abdominal withdrawal reflex score in response to CRD in MS rats was significantly higher with distension pressures of 40, 60, and 80 mmHg. In MS rats, the number of c-fos-like immunoreactive nuclei at dorsal horn of lumbar-sacral spinal cord increased significantly after CRD. 5-HT content in the spinal cord of MS rats was significant higher. In the colon, both 5-HT-positive cell number and 5-HT content were comparable between MS and NH groups before CRD. Post-CRD only MS rats had significant increase in 5-HT content. Protein and mRNA expression levels of 5-HT3 receptors and 5-HT transporter were similar in MS and NH rats. Neonatal maternal separation stress predisposes rats to exaggerated neurochemical responses and visceral hyperalgesia in colon mimicking IBS.