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环境富集通过杏仁中央核中的 GR 介导机制预防慢性应激诱导的脑-肠轴功能障碍。

Environmental enrichment prevents chronic stress-induced brain-gut axis dysfunction through a GR-mediated mechanism in the central nucleus of the amygdala.

机构信息

Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Department of Veterans Affairs Health Care System, Oklahoma City, Oklahoma.

出版信息

Neurogastroenterol Motil. 2020 Jun;32(6):e13826. doi: 10.1111/nmo.13826. Epub 2020 Feb 21.

Abstract

BACKGROUND

Cognitive behavioral therapy (CBT) improves quality of life of patients with irritable bowel syndrome (IBS), a disorder characterized by chronic visceral pain and abnormal bowel habits. Whether CBT can actually improve visceral pain in IBS patients is still unknown. The aim of this study is to evaluate whether environment enrichment (EE), the animal analog of CBT, can prevent stress-induced viscero-somatic hypersensitivity through changes in glucocorticoid receptor (GR) signaling within the central nucleus of the amygdala (CeA).

METHODS

Rats were housed in either standard housing (SH) or EE for 7 days before and during daily water avoidance stress (WAS) exposure (1-h/d for 7 days). In the first cohort, visceral and somatic sensitivity were assessed via visceromotor response to colorectal distention and von Frey Anesthesiometer 24 hous and 21 days after WAS. In another cohort, the CeA was isolated for GR mRNA quantification.

KEY RESULTS

Environment enrichment for 7 days before and during the 7 days of WAS persistently attenuated visceral and somatic hypersensitivity when compared to rats placed in SH. Environment enrichment exposure also prevented the WAS-induced decrease in GR expression in the CeA.

CONCLUSION & INFERENCES: Pre-exposure to short-term EE prevents the stress-induced downregulation of GR, and inhibits visceral and somatic hypersensitivity induced by chronic stress. These results suggest that a positive environment can ameliorate stress-induced pathology and provide a non-pharmacological therapeutic option for disorders such as IBS.

摘要

背景

认知行为疗法(CBT)可改善肠易激综合征(IBS)患者的生活质量,IBS 是一种以慢性内脏疼痛和肠道习惯异常为特征的疾病。CBT 是否真的能改善 IBS 患者的内脏疼痛尚不清楚。本研究旨在评估环境富集(EE),CBT 的动物模拟,是否可以通过改变杏仁中央核(CeA)内的糖皮质激素受体(GR)信号来预防应激引起的内脏躯体感觉过敏。

方法

在每日水回避应激(WAS)暴露(每天 1 小时,持续 7 天)之前和期间,大鼠分别在标准饲养(SH)或 EE 中饲养 7 天。在第一队列中,通过结肠扩张的内脏运动反应和冯弗雷测痛仪在 WAS 后 24 小时和 21 天评估内脏和躯体敏感性。在另一队列中,分离 CeA 以定量 GR mRNA。

主要结果

与 SH 组大鼠相比,WAS 前 7 天和 WAS 期间持续 7 天的 EE 暴露可持久减轻内脏和躯体感觉过敏。EE 暴露还可预防 WAS 诱导的 CeA 中 GR 表达下调。

结论和推论

短期 EE 预暴露可防止应激诱导的 GR 下调,并抑制慢性应激引起的内脏和躯体感觉过敏。这些结果表明,积极的环境可以改善应激引起的病理变化,并为 IBS 等疾病提供非药物治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edd/7906280/b2a1de6308c5/nihms-1671623-f0001.jpg

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