Project/Area Number |
16500250
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
|
Research Institution | National Institute for Basic Biology |
Principal Investigator |
WATANABE Eiji National Institute for Basic Biology, Center for Transgenic Animals and Plants, Associate Professor, 形質転換生物研究施設, 助教授 (30250252)
|
Project Period (FY) |
2004 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | glia / salt / sensor / homeostasis / channel / circumventricular / knockout / culture / 脳室周囲期間 |
Research Abstract |
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.
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