科学家有望找到人类突然入睡的原因
Sudden Sleep
Researchers have spotted a chemical brain process that may explain why some people fall asleep without warning. The research was done in mice, but as this ScienCentral News video reports, it helps explain what regulates our normal sleep patterns and may lead to future treatments for people with narcolepsy.
Sleep Mysteries
At the end of a long day, when fatigue comes wafting over our limbs and starts to tip our lids shut it seems blatantly obvious why we need sleep - we're tired. But surprisingly, why we need sleep and what exactly happens in the brain to trigger sleep is one of the greatest mysteries of neuroscience.
"It's actually the big question - why do we need sleep?" says University of Texas Southwestern Medical Center brain scientist Masashi Yanagisawa, whose research team recently came one step closer to answering that question.
Yanagisawa and his colleagues combined two established scientific techniques to identify and map, for the first time, a prominent sleep circuit in the brains of mice. They say the circuit helps balance sleep patterns in all mammals, including people, though they still don't know what tips that balance to either wake us up or put us to sleep. Yanagisawa hopes his team's map will at least shed new light on sleep's dark mysteries as well as lead to new treatments for people with narcolepsy. "We believe that our research will open up the future avenue for devising a new way of treating various sleep disorders," he says.
Yanagisawa's team focused their research in an area of the brain known to regulate sleep, called the hypothalamus. The hypothalamus is packed with different sleep regulating neurons (nerve cells). The researchers wanted to disentangle one specific set known as "orexin neurons." Orexin neurons are informally called "wake up" neurons because they are brain cells that release a hormone, called orexin, that help keeps people awake. Orexin is a chemical messenger (also known as a neurotransmitter) that travels to different parts of the brain to keep those areas awake, keeping us from falling asleep all the time. People with narcolepsy actually have weak orexin signaling systems.
The research team already knew where these orexin neurons sent their signals, but they didn't know what activated them. To determine their power source, the researchers used a fluorescent green protein, normally found in jellyfish and developed by researchers in France as a tracer molecule. Much like a homing device, if the fluorescent molecule is injected into the brain it will "swim upstream," says Yanagisawa, through the synapses of one orexin neuron to another until it finds the original power source. But because so many different neurons are "just scattered around and completely intermixed" within the tight space of the hypothalamus they needed something even more specific. So the research team genetically modified mice to express the fluorescent molecule wherever orexin neurons were located.
They reported in the journal Neuron that they could finally see a three-part circuit under a fluorescent microscope. The circuit ran between orexin neurons that wake us up and keep us going, histamine neurons that also help keep us awake, and a third group called "cholinergic neurons" or sleep neurons that are active when we are asleep. When the orexin and histamine neurons are active, they turn off the cholinergic or "sleepy neurons," as Yanagisawa calls them. But when the "sleepy neurons" are active they inhibit the orexin and histamine neurons.
"So there is a triangular flip flop or seesaw switch mechanism in our brain which regulates wakefulness and sleep," Yanagisawa explains.
The researchers say this mechanism is important for maintaining sleep homeostasis - basically giving us stable periods of being awake and asleep - but the answer to the big question, what flips the switch on sleep and why we need sleep, is still unknown. They think something builds up in the brain when we are awake, "something we call sleep debt or sleep pressure," says Yanagisawa.
Future Narcolepsy Treatment
In the meantime, the researchers hope their new understanding of this three-part circuit will yield new treatments for people with narcolepsy. Yanagisawa says we may be able to repair failed orexin neurons "with drugs so that in the absence of those functional neurons [they] can still keep awake."
Stasia Wieber, director of the Center for Sleep Medicine at Mount Sinai School of Medicine, in New York, agrees that understanding the orexin signaling system is critical to treating narcolepsy. "Now that we understand a little bit about the feedback mechanisms and loops involved in orexin will only help to be able to use it clinically," she says.
But Wieber also stresses that this research was done in mice and has yet to be reproduced in people. She says it may be five to seven years before it could turn into a medication. For his part, Yanagisawa adds, "We [still] don't know the trigger" for sleep and says finding it will be his next step.
Yanagisawa's research appeared in the April 21, 2005 issue of Neuron and was funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan and ERATO, part of Japan Science and Technology Corporation.
ScienCentral网5月19日消息，科学家通过研究老鼠脑细胞的化学变化过程，有望找到某些人会突然入睡的原因。科学家们对老鼠大脑进行试验后说道，通过此次研究他们有望找到人类控制睡眠的机理，并且找到治疗嗜眠病的方法。
睡眠的秘密
工作了一天之后，人们都会感到疲惫、四肢无力、眼皮也会睁不开。也许这些就是人们需要睡眠的原因。但是，大脑如何触发睡眠机制仍然是人类神经学中的难解之谜。
德克萨斯州立大学脑科研究专家Masashi Yanagisawa说道，“人类为何需要睡眠”长期以来一直困扰着科学家。其研究小组最近的研究为解开这个谜团前进了一大步。
Yanagisawa及其同事研究了老鼠大脑中的“睡眠电路”，哺乳动物大脑中的“睡眠电路”可以帮助它们控制睡眠和苏醒。人类也是如此，具体是如何控制睡眠和苏醒还有待进一步研究。Yanagisawa希望他的研究小组能够找到人类睡眠的机理，并为嗜眠病患者找到治疗方法。他说道，他们的研究会给其它科学家研究人类睡眠混乱铺平道路。
Yanagisawa的小组主要研究老鼠大脑中的下丘脑部分。下丘脑中有许多控制睡眠的神经元。下丘脑中的增食因子(Orexin)神经元会释放出一种称作Orexin的荷尔蒙，这种荷尔蒙可以帮助人们保持苏醒状态。Orexin就像是一个信史，它会传播到大脑各个部分，保持大脑各部分都处于清醒状态。患有嗜眠病的人通常在大脑中都会缺乏orexin神经元。
研究人员已经知道Orexin神经元向大脑哪些部分发送信号，到底是什么激发了Orexin神经元产生这些信号，还是一个谜。为了找到激励源，研究人员使用一种可发光的绿色蛋白质。这种蛋白质首先发现于水母体内，主要用作追踪分子。yanagisawa说道，一旦这种蛋白质被注入大脑中的下丘脑，它就会逆流而上，从一个Orexin神经元游动到另一个，直到游到最初发出信号的源头。但是下丘脑很小，其中不同种类的神经元又很多并且混杂在一起，所以科学家对老鼠的下丘脑作了一定处理后才实施此项试验。
他们在显微镜下最终观察到一个由三部分组成的“信号电路”。连接Orexin神经元的电路保持人们处于清醒状态，组胺神经元也具有同Orexin神经元相似的功能，类胆碱神经元则是当人们处于清醒状态时才处于活动状态，它会使人们处于睡眠状态。Yanagisawa说道，当Orexin神经元和组胺神经元处于活动状态时，它们会抑制类胆碱神经元的活动。同理，当类胆碱神经元处于活动状态时，则会抑制Orexin和组胺神经元的活动。
Yanagisawa解释道，这样以来，大脑中就形成了一个环路，不同的神经元陆续处于活动状态，从而控制动物体的睡眠和苏醒。
研究人员说，这种循环机制对生物体十分重要，它会防止生物体过于劳累。但是大脑如何控制这些神经元的活跃与休眠到目前为止还无人知晓。yanagisawa说道，或许当人们处于清醒状态时，体内的劳累感会不断累积，到达一定程度，自然会触发与促使睡眠有关的神经元。
嗜眠病治疗
研究人员同样希望他们的研究成果为治疗人类嗜眠病提供新的方法。yanagisawa说，医学家可以使用药物修复人体受损伤的Orexin神经元，使它们恢复正常的工作能力。
许多研究人类嗜眠病的科学家也对该研究成果持肯定态度。他们说道，既然人们弄清楚了人类控制睡眠的部分机制，就应该把这些研究成果运用到临床医疗中去。
同时值得注意的是，此项试验只是在老鼠大脑中进行，还没有真正在人脑中进行同样的试验。所以，或许科学家需要五至七年的时间才制造出治疗人类嗜眠病的药物。yanagisawa下一步的研究方向主要集中在弄清楚大脑如何控制神经元交替活动与休眠的触发机制。
