The body's internal clock helps to regulate a water-storing hormone so that nightly dehydration or trips to the toilet are not the norm, research suggests.
In an article published in Nature Neuroscience today, neurophysiologists Eric Trudel and Charles Bourque at the Research Institute of the McGill University Health Centre in Montreal, Canada, propose a mechanism by which the body's circadian system, or internal clock, controls water regulation1. By allowing cells that sense water levels to activate cells that release vasopressin, a hormone that instructs the body to store water, the circadian system keeps the body hydrated during sleep.
"We've known for years that there's a rhythm of vasopressin that gets high when you're sleeping. But no one knew how that occurred. And this group identified a very concrete physiological mechanism of how it occurs," says Christopher Colwell, a neuroscientist who studies sleep and circadian rhythms at the David Geffen School of Medicine at the University of California, Los Angeles.
The body regulates its water content mainly by balancing water intake through thirst with water loss through urine production. People don't drink during sleep, so the body has to minimize water loss to remain sufficiently hydrated. Scientists knew that low water levels excite a group of cells called osmosensory neurons, which direct another set of neurons to release vasopressin into the bloodstream. Vasopressin levels increase during sleep; clock neurons, meanwhile, get quieter.
Trudel and Bourque tested the idea that lower clock-neuron activity might allow osmosensory neurons to more easily activate vasopressin-releasing neurons, which would mean more water retention and less urine production during sleep.
To do this, they isolated thin slices of rat brain containing intact sensory, vasopressin-releasing and clock neurons. Even when removed from the brain, clock neurons continue to mark time.
The duo then stimulated the sensory neurons and recorded any electrical activity in the vasopressin-releasing neurons to monitor communication between the two cell groups. The researchers then moved on to look at the effect of the clock cells on this pathway. When they did not activate the clock cells during the 'sleep' part of their cycle, it was easier for the sensory cells to communicate with vasopressin-releasing cells. Conversely, when they activated the clock cells, this communication decreased markedly.
The results suggest that clock cells function as a dimmer switch for water control. When their activity is high, they prevent sensory cells from instructing secretory cells to release vasopressin. Then, when clock cells are less active, sensory cells can easily instruct secretory cells to release vasopressin, ensuring that the body holds on to its water reserves.
Colwell points out that the study was done in rats, which are nocturnal. Although the vasopressin cycle and clock-neuron activity are similar in rats and humans, the question of whether the same mechanism occurs in animals that sleep at night remains to be answered.
"We show this for this one circuit, but it's possible that clock neurons regulate other circuits in a similar manner and this remains to be studied," says Bourque. He speculates that future studies might reveal whether the same mechanism regulates hunger, sleepiness and other aspects of physiology related to circadian rhythms.
《自然》雜志新聞(NatureNews)安德魯·貝內(nèi)特·赫爾曼(AndrewBennett Hellman)
生物鐘是控制身體水分流失的荷爾蒙調(diào)節(jié)開(kāi)關(guān)。
大腦細(xì)胞使動(dòng)物在睡覺(jué)期間保持水分,而不覺(jué)口渴。
研究顯示,身體內(nèi)部的生物鐘幫助調(diào)節(jié)一種水分儲(chǔ)存荷爾蒙,因此人晚上一般不會(huì)感到口渴或者頻繁上廁所。
“多年來(lái)我們已經(jīng)知道,當(dāng)你在睡覺(jué)時(shí)抗利尿激素的水平會(huì)升高。但是沒(méi)有人知道這是如何發(fā)生的。而這個(gè)研究團(tuán)隊(duì)提出了一種關(guān)于其如何發(fā)生的非常具體的生理機(jī)制,”神經(jīng)科學(xué)家克里斯托弗·科爾韋爾(Christopher Colwell)說(shuō),他在加州大學(xué)洛杉磯分校(UCLA)大衛(wèi)·格芬醫(yī)學(xué)院(DavidGeffen School of Medicine)從事睡眠與晝夜節(jié)律的研究。
身體主要通過(guò)平衡因口渴而飲水與因產(chǎn)生尿液而排水來(lái)調(diào)節(jié)水含量。人們?cè)谒X(jué)時(shí)不會(huì)喝水,所以身體必須使水分流失最小化來(lái)保持充足的水分。科學(xué)家知道低含水量會(huì)激活一組被稱(chēng)為滲透感覺(jué)(osmosensory)神經(jīng)元的細(xì)胞,它們能指示另一組神經(jīng)元以釋放抗利尿激素到血液中。在睡眠期間抗利尿激素水平增加;同時(shí),生物鐘神經(jīng)元變得更加安靜。
特魯?shù)聽(tīng)柡筒紶柨藱z驗(yàn)了這個(gè)想法,即更低的生物鐘神經(jīng)元活動(dòng)可能允許滲透感覺(jué)神經(jīng)元更容易激活抗利尿激素釋放神經(jīng)元,這將意味著在睡眠期間人體會(huì)保存更多的水并產(chǎn)生更少的尿液。
為了檢驗(yàn)這個(gè)想法,他們將小白鼠的大腦分離成薄片,這些薄片仍然包含未受損傷的完整的感覺(jué)神經(jīng)元、抗利尿激素釋放神經(jīng)元和生物鐘神經(jīng)元。即使當(dāng)這些薄片從大腦里取出后,生物鐘神經(jīng)元仍然能夠繼續(xù)記錄時(shí)間。
然后這兩名研究者對(duì)感覺(jué)神經(jīng)元施加刺激,并記錄抗利尿激素釋放神經(jīng)元中的任何電活動(dòng)來(lái)檢測(cè)這兩組細(xì)胞間的溝通。此后,研究者轉(zhuǎn)而考察使用這種方法后生物鐘神經(jīng)元的效應(yīng)。當(dāng)他們未對(duì)處于晝夜周期中“睡眠”時(shí)期的生物鐘細(xì)胞進(jìn)行激活時(shí),感覺(jué)細(xì)胞更容易與抗利尿激素釋放細(xì)胞溝通。相反,當(dāng)他們激活(睡眠時(shí)期的)生物鐘細(xì)胞時(shí),這種溝通明顯下降。
這些結(jié)果指出了生物鐘細(xì)胞作為身體水分控制開(kāi)關(guān)的功能。當(dāng)它們的活動(dòng)很強(qiáng)時(shí),它們阻止感覺(jué)細(xì)胞指示分泌細(xì)胞(secretory cell)去釋放抗利尿激素。相反,當(dāng)生物鐘細(xì)胞激活水平比較弱時(shí),感覺(jué)細(xì)胞能夠更容易地指示分泌細(xì)胞釋放抗利尿激素,以保證身體在睡眠時(shí)保持足夠的蓄水量。
科爾韋爾指出這項(xiàng)研究是在小白鼠上進(jìn)行的,而老鼠恰恰是夜間活動(dòng)動(dòng)物。雖然老鼠和人類(lèi)體內(nèi)的抗利尿激素釋放周期和生物鐘神經(jīng)元活動(dòng)都很相似,但是動(dòng)物夜間睡眠期間是否都發(fā)生了相同的機(jī)制這個(gè)問(wèn)題仍需回答。
“我們只是顯示了這一個(gè)生物反饋回路的結(jié)論,但是可能生物鐘神經(jīng)元也以同樣的方式調(diào)節(jié)其他的反饋回路,這仍需繼續(xù)研究,”布爾克說(shuō)。他預(yù)測(cè)未來(lái)的研究將可能揭示是否相同的機(jī)制也調(diào)節(jié)了饑餓、嗜睡以及與晝夜節(jié)律相關(guān)的其他生理問(wèn)題。