Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats.

IF 2.3 4区 医学 Q2 PSYCHIATRY
Ryoko Hasegawa, Kumi Saito-Nakaya, Li Gu, Motoyori Kanazawa, Shin Fukudo
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引用次数: 0

Abstract

Background: Neonatal maternal separation (MS) has been used to model long-lasting changes in behavior caused by neuroplastic changes associated with exposure to early-life stress. Earlier studies showed that transient gut inflammation can influence the development of irritable bowel syndrome (IBS). A prevailing paradigm of the etiology of IBS is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. This study characterizes the changes in behaviors and neuroendocrine parameters after MS and early-phase trinitrobenzene sulfonic acid (TNBS)-induced colitis. We tested the hypothesis that MS and gut inflammation synergistically induce (1) hyperactivity in male rats and anxiety-like behaviors in female rats and (2) activation of the HPA axis in female rats and deactivation of the HPA axis in male rats after colorectal distention (CRD).

Methods: Male and female rat pups were separated from their dams for 180 min daily from postnatal day (PND) 2 to PND 14 (MS). Early-phase colitis was induced by colorectal administration with TNBS on PND 8. The elevated plus-maze test was performed at 7 weeks. Tonic CRD was performed at 60 mmHg for 15 min at 8 weeks. Plasma ACTH and serum corticosterone were measured at baseline or after the CRD. Analysis of variance was performed for comparison among controls, TNBS, MS, and MS + TNBS.

Results: In male rats, the time spent in open arms significantly differed among the groups (p < 0.005). The time spent in open arms in male MS + TNBS rats was significantly higher than that of controls (p < 0.009) or TNBS rats (p < 0.031, post hoc test). Female rats showed no difference in the time spent in open arms among the groups. MS and gut inflammation induced an increase in plasma ACTH in female rats but not in male rats at baseline.

Conclusions: These findings suggest that MS and gut inflammation synergistically induce hyperactive behavior or exaggerated hypothalamic-pituitary-adrenal axis function depending on sex.

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母性分离和tnbs诱导的肠道炎症协同改变大鼠性别分化应激反应。
背景:新生儿产妇分离(MS)已被用于模拟与暴露于早期生活压力相关的神经可塑性变化引起的长期行为变化。早期的研究表明,短暂的肠道炎症可以影响肠易激综合征(IBS)的发展。肠易激综合征病因学的一个普遍范式是,尽管初始事件完全解决,但短暂的有害事件导致神经疼痛回路的长期敏感化。本研究探讨多发性硬化症和早期三硝基苯磺酸(TNBS)诱导结肠炎后行为和神经内分泌参数的变化。我们验证了MS和肠道炎症协同诱导(1)雄性大鼠多动和雌性大鼠焦虑样行为,(2)雌性大鼠HPA轴激活和雄性大鼠HPA轴失活的假设。方法:从出生后第2天(PND)至第14天(MS),雄性和雌性大鼠幼仔每天与母鼠分离180 min。在PND 8日,结直肠给药TNBS诱导早期结肠炎。7周时进行升高+迷宫试验。在8周时进行60 mmHg的补品CRD,持续15分钟。在基线或CRD后测定血浆ACTH和血清皮质酮。对对照组、TNBS、MS和MS + TNBS进行方差分析比较。结果:在雄性大鼠中,各组之间张开双臂的时间差异显著(p)。结论:这些发现表明MS和肠道炎症协同诱导多动行为或夸大下丘脑-垂体-肾上腺轴功能,这取决于性别。
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来源期刊
CiteScore
3.60
自引率
0.00%
发文量
23
审稿时长
18 weeks
期刊介绍: BioPsychoSocial Medicine is an open access, peer-reviewed online journal that encompasses all aspects of the interrelationships between the biological, psychological, social, and behavioral factors of health and illness. BioPsychoSocial Medicine is the official journal of the Japanese Society of Psychosomatic Medicine, and publishes research on psychosomatic disorders and diseases that are characterized by objective organic changes and/or functional changes that could be induced, progressed, aggravated, or exacerbated by psychological, social, and/or behavioral factors and their associated psychosomatic treatments.
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