The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior
The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior
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DOI：
10.1523/jneurosci.2795-04.2004
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发表时间：
2004-10-20
影响因子：
5.3
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Hiyama, TY;Watanabe, E;Noda, M
脱水引起体液钠（Na）浓度和渗透压的增加。对于体内钠的稳态，控制钠和水的摄入和排泄是至关重要的。然而，大脑中负责控制钠和水摄入行为的感应钠水平的系统仍有待阐明。我们之前报道过Na-x通道优先在大脑的心室周围器官（CVOs）中表达，并且Na-x敲除小鼠在脱水条件下摄入过量的生理盐水。随后，我们证明了Na-x是一个对Na电平敏感的Na通道。在这里，我们表明，表下器官（SFO）是控制盐摄入行为的主要部位，其中Na-x通道是Na水平传感器。向脑室注入高渗钠溶液可引起野生型动物大量饮水和对生理盐水的厌恶，但在敲除小鼠中则没有。重要的是，在两种基因型小鼠中，对盐的厌恶并不是由输注具有生理钠浓度的高渗甘露醇溶液引起的。当用腺病毒表达载体将Nax cDNA引入敲除小鼠的大脑时，只有将Na-x基因转导到CVOs中的SFO的动物在脱水条件下恢复了避盐行为。这些结果清楚地表明，SFO是控制大脑盐摄入行为的中心，其中钠水平敏感的Na-x通道参与感知体液钠水平的生理增加。
Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluid. For Na homeostasis of the body, controls of Na and water intake and excretion are of prime importance. However, the system for sensing the Na level within the brain that is responsible for the control of Na- and water-intake behavior remains to be elucidated. We reported previously that the Na-x channel is preferentially expressed in the circumventricular organs (CVOs) in the brain and that Na-x knock-out mice ingest saline in excess under dehydrated conditions. Subsequently, we demonstrated that Na-x is a Na-level-sensitive Na channel. Here we show that the subfornical organ (SFO) is the principal site for the control of salt-intake behavior, where the Na-x channel is the Na- level sensor. Infusion of a hypertonic Na solution into the cerebral ventricle induced extensive water intake and aversion to saline in wild-type animals but not in the knock-out mice. Importantly, the aversion to salt was not induced by the infusion of a hyperosmotic mannitol solution with physiological Na concentration in either genotype of mice. When Nax cDNA was introduced into the brain of the knock-out mice with an adenoviral expression vector, only animals that received a transduction of the Na-x gene into the SFO among the CVOs recovered salt-avoiding behavior under dehydrated conditions. These results clearly show that the SFO is the center of the control of salt-intake behavior in the brain, where the Na- level-sensitive Na-x channel is involved in sensing the physiological increase in the Na level of body fluids.