Challet E, Bernard D J, Turek F W
Center for Circadian Biology and Medicine, Department of Neurobiology and Physiology, Northwestern University, 2153 North Campus Drive, Evanston, IL 60208,
Brain Res. 1999 Apr 3;824(1):18-27. doi: 10.1016/s0006-8993(99)01192-0.
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.
位于视交叉上核的生物钟受光照强度的24小时变化所调节。然而，当葡萄糖供应减少时，生物钟对光的反应会减弱。我们通过给C57BL/6J小鼠注射金硫葡萄糖（0.6 g/kg）来破坏主要位于腹内侧下丘脑的葡萄糖感受神经元，从而验证了以下假设：腹内侧下丘脑作为整合代谢和激素信号的关键区域，介导了昼夜节律对光反应的代谢调节。在主观夜间中期施加的光脉冲会使处于持续黑暗中的小鼠的运动活动昼夜节律出现相位延迟。如先前观察到的，与自由进食的对照小鼠相比，腹腔注射500 mg/kg 2-脱氧-D-葡萄糖预处理的喂食小鼠以及皮下注射5 IU/kg胰岛素或生理盐水预处理的禁食30小时的低血糖小鼠，光诱导的相位延迟明显减弱。相比之下，与注射金硫葡萄糖并自由进食的小鼠相比，金硫葡萄糖诱导下丘脑损伤的小鼠中类似的代谢挑战并未显著影响光诱导的相位延迟。这些结果表明，腹内侧下丘脑中对金硫葡萄糖敏感的神经元的破坏会在葡萄糖供应不足时阻止昼夜节律对光反应的代谢调节。因此，腹内侧下丘脑可能是协调昼夜节律钟光诱导相移的代谢调节的中心部位。
