Abstract：
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hyperphagia, obesity, developmental delay and intellectual disability. Studies suggest dysfunctional signaling of the neuropeptide oxytocin as one of the key mechanisms in PWS, and administration of oxytocin via intranasal or systemic routes yielded promising results in both humans and mouse models. However, a detailed assessment of the oxytocin system in mouse models of PWS such as the Magel2-deficient Magel2tm1.Stw mouse, is lacking. In the present study, we performed an automated counting of oxytocin cells in the entire paraventricular nucleus of the hypothalamus of Magel2tm1.Stw and wild-type control mice and found a significant reduction in the caudal part, which represents the parvocellular subdivision. In addition, based on the recent discovery that some astrocytes express the oxytocin receptor (OTR), we performed detailed analysis of astrocyte numbers and morphology in various brain regions, and assessed expression levels of the astrocyte marker glial fibrillary acidic protein, which was significantly decreased in the hypothalamus, but not other brain regions in Magel2tm1.Stw mice. Finally, we analyzed the number of OTR-expressing astrocytes in various brain regions and found a significant reduction in the nucleus accumbens of Magel2tm1.Stw mice, as well as a sex-specific difference in the lateral septum. This study suggests a role for caudal paraventricular nucleus oxytocin neurons as well as OTR-expressing astrocytes in a mouse model of PWS, provides novel information about sex-specific expression of astrocytic OTRs, and presents several new brain regions containing OTR-expressing astrocytes in the mouse brain.
摘要：
Prader-Willi综合征（PWS）是一种神经发育障碍，其特征是饮食过多，肥胖，发育迟缓和智力障碍。研究表明，神经肽催产素的功能失调信号是PWS的关键机制之一，通过鼻内或全身途径给予催产素在人和小鼠模型中都产生了有希望的结果。然而,详细评估PWS小鼠模型中的催产素系统，例如Magel2缺陷的Magel2tm1。Stw鼠标,缺乏。在本研究中,我们对Magel2tm1下丘脑整个室旁核中的催产素细胞进行了自动计数。STW和野生型对照小鼠，发现尾部明显减少，代表细胞细分。此外,基于最近发现一些星形胶质细胞表达催产素受体（OTR），我们对不同脑区的星形胶质细胞数量和形态进行了详细分析，并评估星形胶质细胞标志物胶质纤维酸性蛋白的表达水平，下丘脑明显减少，但不是Magel2tm1的其他大脑区域。Stw老鼠。最后,我们分析了不同脑区表达OTR的星形胶质细胞的数量，发现Magel2tm1的伏隔核显著减少。Stw老鼠，以及侧隔的性别差异。这项研究表明，在PWS小鼠模型中，尾脑室旁核催产素神经元以及表达OTR的星形胶质细胞的作用。提供了有关星形胶质细胞OTR的性别特异性表达的新信息，并提出了小鼠大脑中几个新的含有OTR表达星形胶质细胞的大脑区域。
