Corticotropin-releasing hormone mRNA levels in response to chronic mild stress rise in male but not in female rats while tyrosine hydroxylase mRNA levels decrease in both sexes

Corticotropin-releasing hormone mRNA levels in response to chronic mild stress rise in male but not in female rats while tyrosine hydroxylase mRNA levels decrease in both sexes
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DOI:
10.1016/s0306-4530(00)00040-8
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发表时间:
2001-01-01
影响因子:
3.7
通讯作者:
Jezová, D
Jezová, D
中科院分区:
医学2区
文献类型:
--
作者:
Duncko, R;Kiss, A;Jezová, D

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促肾上腺皮质激素释放激素(CRH)和儿茶酚胺在抑郁症的病理生理中起重要作用。在本研究中,我们研究了抑郁症实验模型下丘脑室旁核(PVN)中CRH的基因表达和蓝斑(LC)中酪氨酸羟化酶(TH)的基因表达。采用慢性轻度应激模型对男女大鼠进行为期三周的实验。快乐缺乏行为是抑郁状态的典型标志,通过蔗糖偏好测试来测量。慢性轻度应激导致两性对蔗糖的偏好降低。只有雄性的体重增加减少了。然而,暴露于慢性轻度应激的雄性大鼠在第一分钟的运动活动增强,表明焦虑增加。应激方案结束后第三天测量的基础血浆皮质酮水平、胸腺和肾上腺重量不受应激程序的影响。通过原位杂交对PVN中CRH mRNA水平的评估显示,男性对慢性轻度应激的反应显著升高。在雌性中,CRH mRNA的基础水平高于雄性,但不存在应激诱导的升高。慢性轻度应激导致LC中TH mRNA水平降低。这些数据表明,抑郁症的慢性轻度应激模型诱导了一种特异性应激反应,LC中TH基因表达减少,PVN中体重增加、焦虑样行为和CRH mRNA水平的性别差异明显。(C) 2000 Elsevier Science Ltd.版权所有。
Corticotropin-releasing hormone (CRH) and catecholamines are suggested to play a significant role in the pathophysiology of depression. In the present study we investigated gene expression of CRH in the hypothalamic paraventricular nucleus (PVN) and tyrosine hydroxylase (TH) in the locus coeruleus (LC) in an experimental model of depression. A chronic mild stress model was applied in rats of both genders for a three-week period. Anhedonic behaviour, a typical sign of depression-like state, was measured by a sucrose preference test. The chronic mild stress induced a decrease in sucrose preference in both genders. The body weight gain was reduced in males only. The total activity in the open field test was unchanged, however, male rats exposed to chronic mild stress showed enhanced locomotor activity during the first minute of the session, suggesting increased anxiety. Basal plasma corticosterone levels, thymus and adrenal weights measured on the third day after cessation of the stress regimen, were not affected by the stress procedure. Evaluation of CRH mRNA levels in the PVN by in situ hybridisation revealed a significant rise in response to chronic mild stress in males. In females, the basal CRH mRNA levels were higher compared to those in males, but the stress-induced rise was absent. Chronic mild stress resulted in a decrease in TH mRNA levels in the LC. These data demonstrate that chronic mild stress model of depression induces a specific stress response with a reduction of TH gene expression in the LC and clear gender differences in gain of body weight, anxiety-like behaviour, and CRH mRNA levels in the PVN. (C) 2000 Elsevier Science Ltd. All rights reserved.