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首页> 外文期刊>Brain research >Chronic all-trans retinoic acid administration induces CRF over-expression accompanied by AVP up-regulation and multiple CRF-controlling receptors disturbance in the hypothalamus of rats
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Chronic all-trans retinoic acid administration induces CRF over-expression accompanied by AVP up-regulation and multiple CRF-controlling receptors disturbance in the hypothalamus of rats

机译：慢性全反式维甲酸给药可引起大鼠下丘脑CRF过表达并伴有AVP上调和多种CRF控制受体干扰

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Clinical reports suggest a potential link between excess retinoids and development of depression. Corticotropin-releasing factor (CRF) produced in the hypothalamic paraventricular nucleus (PVN) is considered the central driver of the hypothalamic-pituitary-adrenal (HPA) axis and plays a key role in the pathogenesis of depression. Although we had shown that chronic all-trans retinoic acid (ATRA) administration induced hypothalamic CRF over-expression and hyperactivity of HPA axis in rats, further insight into how ATRA modulate CRF expression is lacking. The activity of CRF neurons is under close control of vasopressinergic system and three-paired receptors (conicosteroid receptors, sex hormone receptors and CRF receptors). Here we show that ATRA-induced CRF over-expression is accompanied by arginine-vasopressin (AVP) up-regulation and apparent gene expression disturbances of CRF-controlling receptors. ATRA was applied to rats by daily intraperitoneal injection for 6 weeks. Chronic ATRA treatment induced significantly increased expression of CRF and AVP in the PVN. Moreover, the transcript levels of CRF receptor 1 (CRFR1), estrogen receptor-beta (ER beta) and mineraloconicoid receptor (MR), three genes involved in the activation of CRF neurons, were significantly increased in the hypothalamus, and the expression ratio of GR alpha/MR was markedly decreased. Correlation analysis indicated that the alteration of multiple CRF-controlling receptors is highly correlated with depression-related behaviors of rats in the forced swimming test. These findings support that in addition to the 'classic' retinoic acid receptor a-mediated transcriptional control of CRF expression, disruption in CRF-modulating systems constitutes a novel pathway that underlies ATRA-induced HPA axis hyperactivity in vivo. (C) 2015 Elsevier B.V. All rights reserved.
机译：临床报告表明，过量的类维生素A与抑郁症的发展之间存在潜在的联系。下丘脑室旁核（PVN）中产生的促肾上腺皮质激素释放因子（CRF）被认为是下丘脑-垂体-肾上腺（HPA）轴的主要驱动力，并且在抑郁症的发病机理中起着关键作用。尽管我们已经证明长期全反式维甲酸（ATRA）诱导大鼠下丘脑CRF过度表达和HPA轴亢进，但仍缺乏对ATRA如何调节CRF表达的深入了解。 CRF神经元的活动受血管加压素系统和三对受体（类固醇激素受体，性激素受体和CRF受体）的紧密控制。在这里，我们显示ATRA诱导的CRF过度表达伴随着精氨酸加压素（AVP）上调和CRF控制受体的明显基因表达障碍。通过每日腹膜内注射将ATRA应用于大鼠，持续6周。慢性ATRA治疗诱导PVN中CRF和AVP的表达显着增加。此外，下丘脑中CRF受体1（CRFR1），雌激素受体-β（ER beta）和矿物质类化合物受体（MR）的转录水平显着升高，这三个基因与CRF神经元的激活有关，其表达比GR alpha / MR明显降低。相关分析表明，在强迫游泳试验中，多种CRF控制受体的改变与大鼠抑郁相关行为高度相关。这些发现支持，除了“经典的”视黄酸受体α介导的CRF表达的转录控制外，CRF调节系统的破坏还构成了一种新的途径，该途径是体内ATRA诱导的HPA轴功能亢进的基础。 （C）2015 Elsevier B.V.保留所有权利。

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