Gold-thioglucose-induced hypothalamic lesions inhibit metabolic modulation of light-induced circadian phase shifts in mice.
Gold-thioglucose-induced hypothalamic lesions inhibit metabolic modulation of light-induced circadian phase shifts in mice.
复制标题
金硫葡萄糖诱导的下丘脑损伤抑制小鼠光诱导昼夜节律相移的代谢调节。
DOI：
10.1016/s0006-8993(99)01192-0
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发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Turek,FW
中科院分区：
文献类型：
--
作者：
Challet,E;Bernard,DJ;Turek,FW
位于视交叉上核的昼夜节律钟被光照强度的24小时变化所携带。然而，当葡萄糖可用性降低时，生物钟对光的反应会降低。我们测试的假设，腹内侧下丘脑，在代谢和激素信号的整合的关键领域，介导的昼夜节律的光反应的代谢调节注射金硫葡萄糖（0.6 g/kg），损害葡萄糖受体神经元，主要位于腹内侧下丘脑C57 BL/6 J小鼠。在主观午夜期间施加的光脉冲诱导保持在恒定黑暗中的小鼠的运动活动的昼夜节律中的相位延迟。如前所述，在用500 mg/kg i. p. 2-脱氧-d-葡萄糖预处理的进食小鼠中以及在用5 IU/kg s.c.胰岛素或盐水，与随意喂食的对照小鼠相比。相比之下，与用金硫葡萄糖处理并随意喂食的小鼠相比，具有金硫葡萄糖诱导的下丘脑病变的小鼠中的类似代谢挑战并未显著影响光诱导的相位延迟。这些结果表明，破坏金硫葡萄糖敏感神经元在下丘脑腹内侧阻止代谢调节的昼夜节律反应的光在葡萄糖供应不足。因此，腹内侧下丘脑可能是协调光诱导的生物钟相移的代谢调节的中心部位。
The circadian clock located in the suprachiasmatic nuclei is entrained by the 24-h variation in light intensity. The clock's responses to light can, however, be reduced when glucose availability is decreased. We tested the hypothesis that the ventromedial hypothalamus, a key area in the integration of metabolic and hormonal signals, mediates the metabolic modulation of circadian responses to light by injecting C57BL/6J mice with gold-thioglucose (0.6 g/kg) which damages glucose-receptive neurons, primarily located in the ventromedial hypothalamus. Light pulses applied during the mid-subjective night induce phase delays in the circadian rhythm of locomotor activity in mice kept in constant darkness. As previously observed, light-induced phase delays were significantly attenuated in fed mice pre-treated with 500 mg/kg i.p. 2-deoxy-d-glucose and in hypoglycemic mice fasted for 30 h, pre-treated with 5 IU/kg s.c. insulin or saline, compared to control mice fed ad libitum. In contrast, similar metabolic challenges in mice with gold-thioglucose-induced hypothalamic lesions did not significantly affect light-induced phase delays compared to mice treated with gold-thioglucose and fed ad libitum. These results indicate that destruction of gold-thioglucose-sensitive neurons in the ventromedial hypothalamus prevent metabolic regulation of circadian responses to light during shortage of glucose availability. Therefore, the ventromedial hypothalamus may be a central site coordinating the metabolic modulation of light-induced phase shifts of the circadian clock.