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

神经垂体激素和生物活性物质在遗传动物模型中对脑功能的新作用

• 批准号: 16390061
• 负责人: UETA Yoichi
• 金额: $ 9.47万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390061/
• 关键词: transgenic rat; vasopressin; oxytocin; GFP; hypothalamus; posterior pituitary gland; peptide; パゾプレッシン; 浸透圧刺激; パッチクランプ法

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.

神经垂体激素（加压素和催产素）在下丘脑的室旁核和视上核的神经分泌细胞中产生，并且它们从垂体后叶的末端分泌到体循环中。加压素是一种抗利尿激素和催产素，参与分娩和排乳反射。最近，我们成功地建立了加压素-GFP转基因大鼠和催产素-CFP转基因大鼠。在荧光显微镜下可观察到加压素分泌神经元发出绿色荧光，催产素分泌神经元发出蓝色荧光。所得结果如下。(1)在转基因大鼠中，加压素-GFP融合基因表现出对盐负荷的夸大反应，而没有扰乱体液稳态。(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，而且还分布在蓝斑等几个脑区。(3)视交叉上核内GFP、加压素和Per 1、2基因表达呈昼夜节律。(4)利用全细胞膜片钳技术研究新型多肽对分离的加压素-GFP神经元的作用是有用的。(5)GFP荧光在线监测系统监测垂体后叶的GFP荧光。接下来，我们计划产生双转基因（加压素-GFP和催产素-CFP）大鼠。

项目成果

Cannabinoids modulate synaptic activity in the rat supraoptic nucleus.

大麻素调节大鼠视上核的突触活动。

• 发表时间: 2005
• 期刊: Journal of Neuroendocrinology 17(9)
• 作者: Soya;A.;Serino;R.;Fujihara;H.;Onaka;T.;Ozaki;Y.;Saito;T.;Nakamura;J.;Ueta.Y.
• 通讯作者: Ueta.Y.

Centrally administered adrenomedullin 2 activates hypothalamic oxytocin-secreting neurons causing elevated plasma oxytosin level in rats.

集中给药的肾上腺髓质素 2 会激活下丘脑催产素分泌神经元，导致大鼠血浆催产素水平升高。

• 发表时间: 2005
• 期刊: American Journal of Physiology 289(5)
• 作者: Hashimoto;H. et al.
• 通讯作者: H. et al.

Galanin-like peptide stimulates vasopressin, oxytocin and ACTH release in rats.

甘丙肽样肽刺激大鼠体内加压素、催产素和促肾上腺皮质激素的释放。

• 发表时间: 2005
• 期刊: Neuroreport 16
• 作者: Hashimoto;M.;Maekawa F;Kuramochi M;Nakata M;Kuramochi M;Kuramochi M;Fujiwara K;Oneka T
• 通讯作者: Oneka T

Neuromedin U has a novel anorexigenic effect independent of the leptin signaling pathway

• DOI: 10.1038/nm1106
• 发表时间: 2004-10-01
• 期刊: NATURE MEDICINE
• 影响因子: 82.9
• 作者: Hanada, R;Teranishi, H;Kojima, M
• 通讯作者: Kojima, M

Centrlly administered neuropeptide W-30 activates magnocellular neurosecretory cells in the supraoptic and paraventricular nuclei with neurosecretion in rats

集中施用神经肽 W-30 通过神经分泌激活视上核和室旁核中的大细胞神经分泌细胞

• 发表时间: 2006
• 期刊: Journal of Endocrinology 190(2)
• 作者: Kawasaki;M;Onaka;T;Nakazato;M;Saito;J;Mera;T;Hashimoto;H;Fujihara;H;Okimoto;N;Ohnishi;H;Nakamura;T;Ueta;Y.
• 通讯作者: Y.