Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice.
Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice.
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DOI：
10.1016/j.ibror.2016.07.001
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发表时间：
2016-12
期刊：
影响因子：
2.6
通讯作者：
Christianson JA
中科院分区：
文献类型：
--
作者：
Fuentes IM;Walker NK;Pierce AN;Holt BR;Di Silvestro ER;Christianson JA
经历早期生活压力可能会通过下丘脑-垂体-肾上腺轴失调导致应激反应失调，并成为发展为慢性盆腔疼痛疾病的危险因素。我们研究了新生儿母体分离（NMS）是否会增加对实验性结肠炎或急性或慢性应激的易感性。雄性小鼠在出生后第 1-21 天接受 NMS，并在成年后评估其旷场行为、后爪敏感性和对结直肠扩张 (CRD) 的内脏运动反应 (VMR)。还在结肠内三硝基苯磺酸（TNBS）治疗或暴露于急性或慢性回避水应激（WAS）之前和之后测量了VMR。测量远端结肠中的髓过氧化物酶（MPO）活性、促炎基因和促肾上腺皮质激素释放因子（CRF）受体表达。基线 VMR 不受 NMS 影响，但接受 CRD 会增加 NMS 小鼠的焦虑样行为和机械后爪敏感性。仅在 NMS 小鼠中，TNBS 治疗剂量依赖性地降低了体重和存活率。 TNBS 治疗后，尽管 MPO 活性增加，但 NMS 小鼠远端结肠中 IL-6 和 artemin mRNA 水平下降。单次 WAS 暴露会增加 NMS 小鼠 CRD 期间的 VMR，并增加初始小鼠远端结肠中的 IL-6 mRNA 和 CRF2 蛋白水平，而 NMS 结肠中的 CRF2 蛋白水平在基线和 WAS 暴露后均升高。总而言之，这些结果表明，小鼠体内的 NMS 破坏了结肠中炎症和应激诱导的基因表达，可能导致小鼠在以后的生活中对特定应激源产生过度反应。新生儿母体分离（NMS）改变了以后生活中对结肠炎症和压力的反应。 NMS 小鼠对 TNBS 结肠炎的敏感性呈剂量依赖性。单次暴露于回避水压力会增加 NMS 小鼠的结直肠敏感性，但不会增加幼稚小鼠的结直肠敏感性。结肠内信号通路的破坏可能导致 NMS 小鼠的易感性增加。
Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS) would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR) to colorectal distension (CRD). VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS) or exposure to acute or chronic water avoidance stress (WAS). Myeloperoxidase (MPO) activity, proinflammatory gene and corticotropin-releasing factor (CRF) receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life. Neonatal maternal separation (NMS) altered responses to colonic inflammation and stress later in life. NMS mice were dose-dependently susceptible to TNBS colitis. A single exposure to water avoidance stress increased colorectal sensitivity in NMS, but not naïve, mice. Disruptions in signaling pathways within the colon may contribute to increased susceptibility in NMS mice.