Studies of sodium-sensing sodium channel in brain

大脑钠感应钠通道的研究

• 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

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.

这里建立了表达小鼠NAX通道的稳定细胞系。在这些细胞中观察到细胞外钠级敏感反应，但在对照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。通过免疫电子显微镜研究，我表明，nax通道蛋白被定位于旋转室中器官中的星形胶质细胞和室心膜细胞的层压过程。该结果表明，神经元 - 胶质传播在大脑的钠感应中起着至关重要的作用。还使用NAX-敲除小鼠研究了大脑的钠感应机制。在脱水下，野生型动物避免摄入高渗钠溶液，而NAX-敲除小鼠在这种情况下继续饮用。将高渗钠溶液输注对小鼠的脑心室，导致野生型小鼠的盐分厌恶行为。另一方面，在NAX-敲除小鼠中未观察到这种厌恶行为。接下来，通过使用腺病毒表达载体将外源性NAX通道引入了NAX-敲除小鼠的环形器官。在脱水条件下，将NAX通道引入亚官方器官的敲除小鼠的避免盐的行为。这些结果表明，亚长卷器官是钠感应的主要基因座，而Nax对于大脑中的钠感应机制是必不可少的。

项目成果

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。

• 发表时间: 2004
• 期刊: Journal of Neuroscience. 24
• 作者: Hiyama TY;et al.
• 通讯作者: et al.

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。

• 发表时间: 2005
• 期刊: Journal of Neuroscience 25
• 作者: Niisako K;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
• 作者: K. Niisato;A. Fujikawa;S. Komai;T. Shintani;E. Watanabe;G. Sakaguchi;G. Katsuura;T. Manabe;M. Noda