Transient gastric irritation in the neonatal rats leads to changes in hypothalamic CRF expression, depression- and anxiety-like behavior as adults.
Transient gastric irritation in the neonatal rats leads to changes in hypothalamic CRF expression, depression- and anxiety-like behavior as adults.
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DOI：
10.1371/journal.pone.0019498
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发表时间：
2011-05-12
期刊：
影响因子：
3.7
通讯作者：
Pasricha PJ
中科院分区：
文献类型：
--
作者：
Liu L;Li Q;Sapolsky R;Liao M;Mehta K;Bhargava A;Pasricha PJ
脑肠轴紊乱是功能性肠病(如肠易激综合征和功能性消化不良)的显著特征，其发病机制通常与心理异常有关。我们假设，这些情况下的心理障碍可能是胃肠道问题造成的，而不是导致它们。以新生大鼠为模型，建立功能性消化不良模型。10日龄雄性SD大鼠给予0.1%碘乙酰胺(IA)或赋形剂灌胃，连续6天。在8-10周龄时，对大鼠进行蔗糖偏好测试和强迫游泳测试，以检查抑郁样行为。采用高架+迷宫、开场和明-暗箱试验测试焦虑样行为。我们还测量了ACTH和皮质酮对小应激源、生理盐水注射和下丘脑CRF表达的反应。行为学测试显示，IA组大鼠的焦虑和抑郁样行为发生了变化，但不是对照组。与对照组相比，IA组大鼠下丘脑和杏仁核CRF免疫反应性、基础血浆皮质酮水平和应激诱导的ACTH水平显著升高。白藜芦醇对大鼠的行为无影响，而CRF 1型受体拮抗剂安塔明可逆转IA大鼠的抑郁样行为。本研究结果提示，新生期短暂的胃刺激可导致抑郁和焦虑样行为的持续增加，CRF在下丘脑的表达增加，HPA轴对应激的敏感性增加。这种抑郁样行为可能是由CRF1受体介导的。这些发现对功能性肠病患者心理共病的发病机制具有重要意义。
A disturbance of the brain-gut axis is a prominent feature in functional bowel disorders (such as irritable bowel syndrome and functional dyspepsia) and psychological abnormalities are often implicated in their pathogenesis. We hypothesized that psychological morbidity in these conditions may result from gastrointestinal problems, rather than causing them. Functional dyspepsia was induced by neonatal gastric irritation in male rats. 10-day old male Sprague-Dawley rats received 0.1% iodoacetamide (IA) or vehicle by oral gavage for 6 days. At 8–10 weeks of age, rats were tested with sucrose preference and forced-swimming tests to examine depression-like behavior. Elevated plus maze, open field and light-dark box tests were used to test anxiety-like behaviors. ACTH and corticosterone responses to a minor stressor, saline injection, and hypothalamic CRF expression were also measured. Behavioral tests revealed changes of anxiety- and depression-like behaviors in IA-treated, but not control rats. As compared with controls, hypothalamic and amygdaloid CRF immunoreactivity, basal levels of plasma corticosterone and stress-induced ACTH were significantly higher in IA-treated rats. Gastric sensory ablation with resiniferatoxin had no effect on behaviors but treatment with CRF type 1 receptor antagonist, antalarmin, reversed the depression-like behavior in IA-treated rats The present results suggest that transient gastric irritation in the neonatal period can induce a long lasting increase in depression- and anxiety-like behaviors, increased expression of CRF in the hypothalamus, and an increased sensitivity of HPA axis to stress. The depression-like behavior may be mediated by the CRF1 receptor. These findings have significant implications for the pathogenesis of psychological co-morbidity in patients with functional bowel disorders.
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影响因子：
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