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Studies of sodium-sensing sodium channel in brain

大脑钠感应钠通道的研究

基本信息

批准号：
16500250
负责人：
WATANABE Eiji
金额：
$ 2.3万
依托单位：
National Institute for Basic Biology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500250/
关键词：
glia salt sensor homeostasis channel circumventricular knockout culture 脳室周囲期間

项目摘要

Stable cell lines which express mouse Nax channel were established here. The extracellular sodium-level sensitive response was observed in these cells, but not in control Nax-negative cells. These cell lines are useful for functional studies of molecular and cellular mechanisms of Nax channel. By immuno-electron microscopic studies, I showed that Nax channel protein was localized to laminate processes of astrocytes and ependymal cells in the circumventricular organs. This result suggests that neuron-glia communication plays crucial role in the sodium sensing of the brain. Sodium sensing mechanism of the brain was also studied using by the Nax-knockout mice. Under dehydration, wild-type animals avoid intake of hypertonic sodium solution, whereas the Nax-knockout mice keep drinking it under such conditions. Infusion of hypertonic sodium solution to the cerebral ventricle of mice caused aversive behavior for salt-intake in wild-type mice. On the other hand, such aversive behavior was not observed in Nax-knockout mice. Next, exogenous Nax channel was introduced to the circumventricular organs of the Nax-knockout mice by using Adenoviral expression vector. The introduction of Nax channel to the subfornical organ recovered the salt-avoiding behavior of the knockout mice under dehydrated conditions. These results indicate that the subfornical organ is the dominant locus of the sodium sensing and that Nax is indispensable for the sodium-sensing mechanism in the brain.

建立了稳定表达小鼠NAX通道的细胞系。在这些细胞中观察到了细胞外钠水平的敏感反应，但在对照的Nax阴性细胞中没有观察到。这些细胞系可用于NAX通道分子和细胞机制的功能研究。免疫电子显微镜研究表明，Nax通道蛋白定位于室周器官内星形胶质细胞和室管膜细胞的层状突起。这一结果表明，神经元-神经胶质细胞的通讯在大脑的钠感觉中起着至关重要的作用。并利用Nax基因敲除小鼠研究了脑组织的钠敏感机制。在脱水状态下，野生型动物避免摄入高渗钠溶液，而NAX基因敲除小鼠在这种情况下继续饮用高渗钠溶液。向小鼠脑室注入高渗钠溶液可引起野生型小鼠对盐摄取的厌恶行为。另一方面，在NAX基因敲除的小鼠中没有观察到这种厌恶行为。接下来，用腺病毒表达载体将外源Nax通道导入Nax基因敲除小鼠的脑室周围器官。将Nax通道引入穹隆下器，恢复了基因敲除小鼠在脱水条件下的避盐行为。这些结果表明，穹隆下器是钠敏感的主要部位，Nax在脑内钠敏感机制中是不可或缺的。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The subfomical organ is primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior.

窝下器官是 Nax 钠通道感测钠水平的主要场所，用于控制盐摄入行为。

DOI：
发表时间：
2004
期刊：
Journal of Neuroscience. 24
影响因子：
0
作者：
Hiyama TY;et al.
通讯作者：
et al.

The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior

DOI：
10.1523/jneurosci.2795-04.2004
发表时间：
2004-10-20
期刊：
JOURNAL OF NEUROSCIENCE
影响因子：
5.3
作者：
Hiyama, TY;Watanabe, E;Noda, M
通讯作者：
Noda, M

Age-Dependent Enhancement of Hippocampal Long-Term Potentiation and Impairment of Spatial Learning through the Rho-Associated Kinase Pathway in Protein Tyrosine Phosphatase Receptor Type Z-Deficient Mice

DOI：
10.1523/jneurosci.2565.04.2005
发表时间：
2005-02
期刊：
The Journal of Neuroscience
影响因子：
0
作者：
K. Niisato;A. Fujikawa;S. Komai;T. Shintani;E. Watanabe;G. Sakaguchi;G. Katsuura;T. Manabe;M. Noda
通讯作者：
K. Niisato;A. Fujikawa;S. Komai;T. Shintani;E. Watanabe;G. Sakaguchi;G. Katsuura;T. Manabe;M. Noda

Age-dependent enhancement of hippocampal long-term ostentation and impairment of spatial leaming through the Rho-associated kinas pathway in protein tyrosine phosphates receptor receptor type Z-deficient mice.

在蛋白酪氨酸磷酸盐受体受体 Z 型缺陷小鼠中，通过 Rho 相关激酶途径，海马长期表现的年龄依赖性增强和空间学习的损害。