Hypothalamic-pituitary-adrenal axis hyperactivity accounts for anxiety- and depression-like behaviors in rats perinatally exposed to bisphenol A.
Hypothalamic-pituitary-adrenal axis hyperactivity accounts for anxiety- and depression-like behaviors in rats perinatally exposed to bisphenol A.
复制标题
下丘脑-垂体-肾上腺轴过度活跃导致围产期暴露于双酚 A 的大鼠出现焦虑和抑郁样行为
DOI：
10.7555/jbr.29.20140058
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发表时间：
2015-05
影响因子：
2.3
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Chen F;Zhou L;Bai Y;Zhou R;Chen L
大量研究表明，围产期环境剂量暴露可引起大鼠焦虑/抑郁相关行为的长时程增强。下丘脑-垂体-肾上腺（HPA）轴的过度活跃是焦虑和抑郁相关疾病中最一致的生物学发现之一。据报道，HPA轴易受发育重编程的影响。本研究的重点是在出生后一天（PND）80雄性大鼠围产期暴露于环境剂量BPA的HPA反应。雌性种鼠从妊娠第10天至哺乳第7天经口给予2 μg/（kg. d）BPA，其子代（PND 80 BPA暴露大鼠）表现出明显的焦虑/抑郁样行为。 值得注意的是，显着增加血清皮质酮和促肾上腺皮质激素，促肾上腺皮质激素释放激素的mRNA检测BPA暴露大鼠之前或之后的轻度应激。此外，BPA暴露大鼠海马中糖皮质激素受体mRNA的水平降低，但下丘脑没有。BPA暴露大鼠海马盐皮质激素受体mRNA、神经元型一氧化氮合酶和磷酸化cAMP反应元件结合蛋白水平升高。此外，BPA暴露大鼠的睾酮水平。结果表明，重编程诱导的HPA轴活动过度是围产期BPA暴露与焦虑和抑郁症持续增强之间的重要联系。
Abstract Accumulating studies have proved that perinatal exposure to environmental dose causes long-term potentiation in anxiety/depression-related behaviors in rats. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent biological findings in anxiety- and depression-related disorders. The HPA axis is reported to be susceptible to developmental reprogramming. The present study focused on HPA reactivity in postnatal day (PND) 80 male rats exposed perinatally to environmental-dose BPA. When female breeders were orally administered 2 μg/(kg.day) BPA from gestation day 10 to lactation day 7, their offspring (PND 80 BPA-exposed rats) showed obvious anxiety/depression-like behaviors. Notably, significant increase in serum corticosterone and adrenocorticotropin, and corticotropin-releasing hormone mRNA were detected in BPA-exposed rats before or after the mild stressor. Additionally, the level of glucocorticoid receptor mRNA in the hippocampus, but not the hypothalamus, was decreased in BPA-exposed rats. The levels of hippocampal mineralocorticoid receptor mRNA, neuronal nitric oxide synthase and phosphorylated cAMP response element binding protein were increased in BPA-exposed rats. In addition, the testosterone level was in BPA-exposed rats. The results indicate that reprogramming-induced hyperactivity of the HPA axis is an important link between perinatal BPA exposure and persistent potentiation in anxiety and depression.