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首页> 外文期刊>The European Journal of Neuroscience >Overexpression of corticotropin-releasing hormone in transgenic mice and chronic stress-like autonomic and physiological alterations.
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Overexpression of corticotropin-releasing hormone in transgenic mice and chronic stress-like autonomic and physiological alterations.

机译：转基因小鼠中促肾上腺皮质激素释放激素的过度表达以及慢性应激样的自主神经和生理改变。

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To gain a greater insight into the relationship between hyperactivity of the corticotropin-releasing hormone (CRH) system and autonomic and physiological changes associated with chronic stress, we developed a transgenic mouse model of central CRH overproduction. The extent of central and peripheral CRH overexpression, and the amount of bioactive CRH in the hypothalamus were determined in two lines of CRH-overexpressing (CRH-OE) mice. Furthermore, 24 h patterns of body temperature, heart rate, and activity were assessed using radiotelemetry, as well as cumulative water and food consumption and body weight gain over a 7-day period. CRH-OE mice showed increased amounts of CRH peptide and mRNA only in the central nervous system. Despite the presence of the same CRH transgene in their genome, only in one of the two established lines of CRH-OE mice (line 2122, but not 2123) was overexpression of CRH associated with increased levels of bioactive CRH in the hypothalamus, increased body temperature and heart rate (predominantly during the light (inactive) phase of the diurnal cycle), decreased heart rate variability during the dark (active) phase, and increased food and water consumption, when compared with littermate wildtype mice. Because line 2122 of the CRH transgenic mice showed chronic stress-like neuroendocrine and autonomic changes, these mice appear to represent a valid animal model for chronic stress and might be valuable in the research on the consequences of CRH excess in situations of chronic stress.
机译：为了更深入地了解促肾上腺皮质激素释放激素（CRH）系统的过度活跃与与慢性应激相关的自主神经和生理变化之间的关系，我们开发了中央CRH过度生产的转基因小鼠模型。在两条CRH过表达（CRH-OE）小鼠系中确定下丘脑中枢和外周CRH过表达的程度以及生物活性CRH的量。此外，使用无线电遥测技术评估了24小时的体温，心率和活动模式，以及在7天的时间内累积的水和食物消耗以及体重增加。 CRH-OE小鼠仅在中枢神经系统中显示出增加的CRH肽和mRNA含量。尽管它们的基因组中存在相同的CRH转基因，但只有在两个已建立的CRH-OE小鼠系之一（2122系，但不是2123系）中，CRH的过度表达与下丘脑中生物活性CRH的水平升高相关，从而增加了机体与同窝野生型小鼠相比，温度和心率（主要在昼夜周期的轻（非活动）阶段），黑暗（活动）阶段心率变异性降低以及食物和水的消耗增加。因为CRH转基因小鼠的2122品系显示出类似慢性应激的神经内分泌和自主神经变化，所以这些小鼠似乎代表了一种有效的慢性应激动物模型，并且在研究慢性应激情况下CRH过量的后果方面可能具有重要的价值。

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