Urocortin 3 Modulates Social Discrimination Abilities via Corticotropin-Releasing Hormone Receptor Type 2
Urocortin 3 Modulates Social Discrimination Abilities via Corticotropin-Releasing Hormone Receptor Type 2
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DOI：
10.1523/jneurosci.1049-10.2010
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发表时间：
2010-07-07
影响因子：
5.3
通讯作者：
Wurst, Wolfgang
中科院分区：
文献类型：
--
作者：
Deussing, Jan M.;Breu, Johannes;Wurst, Wolfgang
尿皮质素 3 (UCN3) 在啮齿类动物大脑的特定核团中强烈表达，其位点与表达尿皮质素 1 和尿皮质素 2（促肾上腺皮质激素释放激素受体 2 型 (CRH-R2) 的其他内源性配体）的位点不同。为了确定 UCN3 的生理作用，我们培育了 UCN3 缺陷小鼠，其中 UCN3 开放阅读框被 tau-lacZ 报告基因取代。通过该报告基因，臂旁核和前乳头核被鉴定为以前未知的 UCN3 表达位点。此外，引入的报告基因使得表达UCN3的神经元的轴突投影分别从上橄榄核旁核到下丘以及从内侧杏仁核后背部分到终纹床核主核的轴突投影得以可视化。对整个大脑 tau-lacZ 报告基因活性的检查强调了 UCN3 在与辅助嗅觉系统功能相连的细胞核中的主要表达。对雄性和雌性小鼠进行了全面的表型分析，但没有一项应用测试表明 UCN3 在下丘脑-垂体-肾上腺皮质轴调节、焦虑或抑郁相关行为中的作用。然而，受整个辅助嗅觉系统普遍表达的启发，我们发现雄性和雌性 UCN3 敲除小鼠的社会辨别能力发生了变化，这种变化也存在于雄性 CRH-R2 敲除小鼠中。总之，我们的结果表明 UCN3 和 CRH-R2 与社会线索的处理和社会记忆的建立有关的新作用。
Urocortin 3 (UCN3) is strongly expressed in specific nuclei of the rodent brain, at sites distinct from those expressing urocortin 1 and urocortin 2, the other endogenous ligands of corticotropin-releasing hormone receptor type 2 (CRH-R2). To determine the physiological role of UCN3, we generated UCN3-deficient mice, in which the UCN3 open reading frame was replaced by a tau-lacZ reporter gene. By means of this reporter gene, the nucleus parabrachialis and the premammillary nucleus were identified as previously unknown sites of UCN3 expression. Additionally, the introduced reporter gene enabled the visualization of axonal projections of UCN3-expressing neurons from the superior paraolivary nucleus to the inferior colliculus and from the posterodorsal part of the medial amygdala to the principal nucleus of the bed nucleus of the stria terminalis, respectively. The examination of tau-lacZ reporter gene activity throughout the brain underscored a predominant expression of UCN3 in nuclei functionally connected to the accessory olfactory system. Male and female mice were comprehensively phenotyped but none of the applied tests provided indications for a role of UCN3 in the context of hypothalamic-pituitary-adrenocortical axis regulation, anxiety-or depression-related behavior. However, inspired by the prevalent expression throughout the accessory olfactory system, we identified alterations in social discrimination abilities of male and female UCN3knock-out mice that were also present in maleCRH-R2knock-out mice. In conclusion, our results suggest a novel role forUCN3and CRH-R2 related to the processing of social cues and to the establishment of social memories.