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頭腦中年輕的源泉

Dracula(那個著名的吸血鬼)也許真的說對了一件事情:年輕的血液可以修復(fù)一個年老的身軀??茖W(xué)家們已經(jīng)發(fā)現(xiàn)一只三個月大的老鼠的血液可以慢慢的使一只年老的老鼠的大腦重造新的腦細(xì)胞。他們還沒有確定重新變年輕的因素,但是他們發(fā)現(xiàn)了一種血液中的化合物似乎會促進(jìn)大腦衰老。

As the body ages, the brain gradually becomes more sluggish. Even in people lucky enough to dodge neurodegenerative disorders such as Alzheimer's disease, fewer new neurons are created from stem cells in the brain, and the activity of existing neurons weakens. Neuroscientist Tony Wyss-Coray of Stanford University School of Medicine in Palo Alto, California, suspected that the changes could be mediated by factors in the blood.

隨著身體變老,大腦會逐漸變遲鈍。即使在那些幸免于神經(jīng)退化性疾病(例如老年癡呆癥)的人之中,也很少有新的神經(jīng)元從大腦的原細(xì)胞中再被創(chuàng)造出來,而且已經(jīng)存在的神經(jīng)元也會逐漸的變?nèi)?。來自加州圣保羅斯坦福醫(yī)藥學(xué)院的神經(jīng)科學(xué)家Tony Wyss Coray猜想這些衰老變化也許可以被血液中的某些因素調(diào)停緩和。

Previous research has shown that giving young blood to older mice boosts their immune system and muscle function. Wyss-Coray wondered whether the same might be true in the brain. Although the so-called blood-brain barrier blocks many large molecules from entering the brain from the bloodstream, the barrier isn't sealed tight everywhere, which might allow some compounds to get through. It's leakiest at places where there are brain stem cells, suggesting that these neuron precursors may have interaction with the circulatory system.

以前的一些研究顯示給老老鼠注射年輕老鼠血液會激發(fā)老老鼠的免疫系統(tǒng)和肌肉功能。Wyss Coray就想這個現(xiàn)象會不會也出現(xiàn)在大腦中。雖然血液大腦界限阻隔了很多血液中的大分子進(jìn)入大腦,但這層界限不是在所有地方都密封得很好的,這就有機(jī)會讓某些混合物通過。這些界限在大腦原細(xì)胞處尤其密封性的不好,暗示著這些神經(jīng)元前體也許有機(jī)會和循環(huán)系統(tǒng)接觸。

Wyss-Coray's team measured neurogenesis, the creation of new neurons from stem cells, in mice that were 3 months old and mice that were almost 2 years old and considered adults. Then they surgically connected the circulatory systems of pairs of young and old mice. The number of new cells in one region of the brain's hippocampus, related to memory formation, went from fewer than 400 to almost 1000 in the older mice. In the younger mice, it dropped by almost a quarter, the scientists report today in Nature. "It worked in both directions," says Wyss-Coray. "The age of the blood has a special effect on the brain."

Wyss Coray的團(tuán)隊(duì)測量了三個月大的老鼠和大概有兩歲大的老鼠的神經(jīng)形成---就是新的神經(jīng)元細(xì)胞從原細(xì)胞中產(chǎn)生的過程。然后他們用手術(shù)辦法把年輕老鼠和老老鼠的循環(huán)系統(tǒng)連接起來。研究者在自然雜志中說:老老鼠大腦中的海馬體---一種和記憶形成有關(guān)的組織---里面的新細(xì)胞從少于400個暴漲到將近1000個,而年輕老鼠的新細(xì)胞幾乎下降了1/4。“這是雙向運(yùn)作的”,Wyss Coray說,“血液的年齡對大腦有特殊影響”。

When the researchers gave young mice daily injections of older blood, not only did neurogenesis decrease, but their learning and memory scores in a water maze test got worse. They made more than twice the number of mistakes in the maze after a day of training and a day of testing.

當(dāng)研究者們每天把老的血液注入年輕老鼠中,年輕老鼠下降的不只有神經(jīng)形成,他們在水迷宮測試中表現(xiàn)出的的學(xué)習(xí)和記憶能力也會變差。經(jīng)過一天訓(xùn)練和一天測試,他們比原來(沒被注射的正常年輕老鼠)多犯了一倍的錯誤。

To isolate the compound responsible for these changes, Wyss-Coray and his colleagues focused on 66 blood-borne chemicals. They identified 17 that increased in concentration as a mouse aged. One of them, a protein called CCL11, was enough to slow neurogenesis when injected into the bloodstream on its own. The researchers haven't yet found a compound that does the reverse—turning up neurogenesis. But finding more neurogenesis in old mice given young blood suggests that it exists.

為了隔離出導(dǎo)致這些改變的混合物,Wyss Coray和他的同事把目標(biāo)鎖定在血液中的66種化學(xué)品。他們確認(rèn)了17種隨著年齡增長而增長的化合物。其中一種叫CCL11的蛋白質(zhì),足以在單獨(dú)被注射入血液的情況下導(dǎo)致神經(jīng)形成減緩。研究者們還沒有找到一種能起到相反效果---加快神經(jīng)形成的化合物。但是被注射了年輕血液后老老鼠體內(nèi)形成了更多神經(jīng)元這一現(xiàn)象暗示了這種化合物的存在。

The findings offer a proof of principle that neurogenesis can be controlled through the blood, a paradigm-shifting idea for treating neurodegenerative disease, Wyss-Coray says. "The big implication here is that we can potentially affect brain aging and degradation, even dementia, by targeting factors in the periphery rather than having to target the brain directly."

這些發(fā)現(xiàn)證明了神經(jīng)形成這一過程可以通過血液控制的原理,這一原理會是對治療神經(jīng)退化性疾病一個思考模式的轉(zhuǎn)移。Wyss Coray 說“大畫面是我們可以通過控制邊緣因素而不是大腦本身來影響大腦的老化和退化,甚至癡呆程度”。

Richard Ransohoff, a neuroscientist at the Cleveland Clinic in Ohio, says the new study is a leap toward understanding how neurogenesis is controlled in the adult brain. "I think it's very exciting to know that the aging stem cell population can remain responsive to environmental cues." But more work is needed to fully understand how all the cues work, he says, and whether the findings hold true in people.

Richard Ransohoff,俄亥俄克利夫蘭診所的神經(jīng)學(xué)家,說這個新的發(fā)現(xiàn)是對于成熟大腦中神經(jīng)形成方式了解的一大步飛躍。“我認(rèn)為能知道老化的原細(xì)胞還會對外界誘因有所反應(yīng)這一點(diǎn)是很令人興奮的”。但是還需要進(jìn)一步地研究具體這些誘因有何作用,他說,還有這些結(jié)果在人體內(nèi)是否適用。

"One of the next steps is to take these factors and measure them in aging humans," Ransohoff says. "You might take patients with neurodegenerative diseases and see how the factors are different, or follow how they change over time in people with early cases of disease."

“接下來的一步就是在人體內(nèi)發(fā)現(xiàn)并測量這些因素”,Ransohoff說,“你可以試驗(yàn)一下有神經(jīng)退化疾病的病人,然后看這些因素有什么不同,也可以追蹤這些因素從輕度神經(jīng)退化到嚴(yán)重的過程中是如何變化的”。

Wyss-Coray plans to start out by analyzing more blood-borne factors in mice. His team is planning a screen of hundreds more factors to see what else may be controlling the aging of the brain.

Wyss Coray計(jì)劃先分析老鼠體內(nèi)更多的血液因素,他的團(tuán)隊(duì)計(jì)劃著掃描幾百個其他因素來看還有沒有其他因素也對大腦老化起著決定性作用。

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