Novel roles of neurohypophyseal hormones and biological active substances on brain function in genetic animal model

神经垂体激素(加压素和催产素)是在下丘脑室旁核和视上核的神经分泌细胞中产生的，它们从垂体后叶的末端分泌到全身循环中。已知加压素是一种抗利尿激素，催产素S参与分娩和排乳反射。最近，我们成功地获得了加压素-GFP转基因大鼠和催产素-CFP转基因大鼠。在荧光显微镜下，可以观察到加压素分泌神经元的绿色荧光和催产素分泌神经元的蓝色荧光。所获得的结果如下。(1)在转基因大鼠中，血管加压素-GFP融合基因对盐负荷的反应过度，不影响体液稳态。(2)在秋水仙素处理的加压素-GFP转基因大鼠中，GFP荧光不仅分布在下丘脑-神经垂体系统，而且在蓝斑等脑区也有分布。(3)视交叉上核内GFP、加压素和PER1、2的基因表达呈昼夜节律。(4)应用全细胞膜片钳技术研究了新型多肽对分离的加压素-GFP神经元的作用。(5)用GFP在线监测系统监测垂体后叶的GFP荧光。下一步，我们计划产生双转基因(加压素-GFP和催产素-CFP)大鼠。

Neurohypophyseal hormones (vasopressin and oxytocin) are produced in the neurosecretory cells in the paraventricular and supraoptic nuclei of the hypothalamus, and they are secreted into the systemic circulation from the terminals of the posterior pituitary gland. Vasopressin is known to be anti-diuretic hormone and oxytociin s involved in the delivery and milk-ejection reflex. Recently, we succeeded to generate vasopressin-GFP transgenic rats and oxytocin-CFP transgenic rats. Under fluorescent microscopy we can observe green fluorescence in vasopressin-secreting neurons and blue fluorescence in oxytocin-secreting neurons. The obtained results are as follow. (1) The vasopressin-GFP fusion gene showed exaggerated response to salt loading without disturbance of body fluid homeostasis in the transgenic rats. (2) The GFP fluorescence was distributed in not only the hypothalamo-neurohypophyseal system but also several brain areas such as the locus coeruleus in colchicines-treated vasopressin-GFP transgenic rats. (3) The gene expression of GFP as well as vasopressin and Per1, 2 in the suprachiasmatic nucleus showed circadian rhythm. (4) It was useful to examine the effects of novel peptides on isolated vasopressin-GFP neuron, by using whole-cell patch-clamp technique. (5) The GFP fluorescence in the posterior pituitary gland was monitored by online GFP-monitoring system. Next, we make a plan to generate double transgenic (vasopressin-GFP and oxytocin-CFP) rats.