动物包括人的昼夜节律是靠什么机制控制的?


动物包括人的昼夜节律是靠什么机制控制的?
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十五年前,一种奇怪的突变果蝇,引起了美国西北大学昼夜节律研究专家Ravi Allada博士的注意和好奇,最近,他带领的神经科学家小组发现了“动物的生物钟如何在早上叫醒它,而在夜间使其入睡”。这项研究结果发表在八月十三日的国际顶级杂志《Cell》。

其实,生物钟的机制很像一个光开关。在一项脑节律神经元(支配着日间睡眠-觉醒周期)的研究中,Allada和他的研究团队发现,在白天,这些神经元中的钠离子通道活性很高,可打开细胞,并最终唤醒动物,在夜间,较高的钾离子通道活性可关闭细胞,使动物进入睡眠。通过进一步调查,研究人员惊奇地发现,在果蝇和小鼠中有着相同的睡眠-觉醒开关。

本文资深作者、Weinberg艺术与科学学院神经生物学教授Allada说:“这表明,我们睡眠-觉醒周期的控制机制是古老的。在几百年的演变中,这种振荡机制似乎是保守的。如果它存在于小鼠身上,它也可能存在于人类中。”

更好地理解这一机制,可能会带来新的药物靶点,以解决时差、轮班工作相关的睡眠-觉醒问题,以及生物钟引发的其他问题。最后,我们就有可能重置一个人的内部时钟,以适应他的情况。

研究人员将其称作一种“自行车”机制:两个踏板,在24小时内上上下下,向神经元传递重要的时间信息。研究人员意外地发现,两个踏板——钠离子流和钾离子流,不论在简单的果蝇,还是在更复杂的小鼠当中,都是活跃的。

本文第一作者Matthieu Flourakis说:“令人惊奇的是,在昆虫和哺乳动物中发现的睡眠周期控制机制,是一样的。小鼠是夜间活动的,果蝇是白天活动的,但是它们的睡眠周期是以同样的方式受到控制。”

当他加入Allada的团队后,Flourakis想知道,果蝇昼夜节律的神经元活动,是否随一天中的时间变化而改变。在神经生物学系Indira M. Raman教授的帮助下,他发现了很强的节律:神经元在早晨更加兴奋,而在晚上却不太活跃。

研究人员接下来想知道这是为什么。他们发现,当钠离子流很高时,神经元更加活跃,使动物觉醒,当钾离子流很高时,神经元安静下来,导致动物处于睡眠状态。钠离子流和钾离子流之间的平衡,控制着动物的昼夜节律。

然后,Flourakis、Allada和他们的同事想知道,这样一个过程是否也存在于更接近人类的动物中。他们研究了小鼠大脑中控制动物昼夜节律的一个小区域——视交叉上核,由20000个神经元组成,并发现了同样的机制。
Allada说:“这项研究花了很长时间,但我们能够把基因组学、遗传学、行为学研究和神经元活动的电测量结合在一起。”他说,当然,现在我们有关于“什么调节着这种睡眠-觉醒途径”的更多问题,所以还需要开展更多的工作。
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