學(xué)習(xí)記憶易受創(chuàng)，短期壓力勿小覷

Short-term stress lasting as little as a few hours can impair brain-cell communication in areas associated with learning and memory, University of California, Irvine researchers have found.

It has been known that severe stress lasting weeks or months can impair cell communication in the brain's learning and memory region, but this study provides the first evidence that short-term stress has the same effect.

"Stress is a constant in our lives and cannot be avoided," said Dr. Tallie Z. Baram, the Danette Shepard Chair in Neurological Sciences in the UC Irvine School of Medicine and study leader. "Our findings can play an important role in the current development of drugs that might prevent these undesirable effects and offer insights into why some people are forgetful or have difficulty retaining information during stressful situations."

In their study, Baram and her UC Irvine colleagues identified a novel process by which stress caused these effects. They found that rather than involving the widely known stress hormone cortisol, which circulates throughout the body, acute stress activated selective molecules called corticotropin releasing hormones, which disrupted the process by which the brain collects and stores memories.

Learning and memory take place at synapses, which are junctions through which brain cells communicate. These synapses reside on specialized branchlike protrusions on neurons called dendritic spines.

In rat and mouse studies, Baram's group saw that the release of CRH in the hippocampus, the brain's primary learning and memory center, led to the rapid disintegration of these dendritic spines, which in turn limited the ability of synapses to collect and store memories.

The researchers discovered that blocking the CRH molecules' interaction with their receptor molecules eliminated stress damage to dendritic spines in the hippocampal cells involved with learning and memory.

In addition, the authors replicated the effects of stress on dendritic spines by administering low levels of synthetic CRH, and watching how the spines retracted over minutes. "Fortunately, once we removed the CRH, the spines seemed to grow back," Baram said.

Baram also noted that there are compounds under development that show the ability to block CRH receptors, and that this study can play a role in the creation of therapies based on these compounds to address stress-related learning and memory loss.

The study appears in the March 12 edition of the Journal of Neuroscience. Yuncai Chen, Celine Dubé and Courtney Burgdorff of UC Irvine also participated in the study, which was supported by the National Institutes of Health.

加州大學(xué)歐文分校研究人員發(fā)現(xiàn)，即使只是幾小時(shí)的短期壓力也擾亂腦細(xì)胞間的正常運(yùn)作，而這些運(yùn)作正關(guān)系到學(xué)習(xí)和記憶。

我們知道，持續(xù)長達(dá)幾周甚至幾個(gè)月的強(qiáng)大壓力會(huì)對(duì)大腦學(xué)習(xí)和記憶區(qū)域的神經(jīng)細(xì)胞傳導(dǎo)造成損害。但是這次實(shí)驗(yàn)第一次發(fā)現(xiàn)，短期壓力也會(huì)產(chǎn)生同樣的破壞力。

加州大學(xué)歐文分校醫(yī)學(xué)院神經(jīng)科學(xué)Danette Shepard 主席，這次研究的領(lǐng)導(dǎo)者，Tallie Z. Baram博士說道：“我們的生活中到處都存在著壓力，躲也躲不了。我們這次的研究成果將起到非常重要的作用。根據(jù)這些研究成果，我們可以制造新的藥物以減輕不良影響，并且深入探究有些人為什么在壓力下容易健忘或者記憶力出現(xiàn)問題。”

在這次研究中，Baram及他的同事還發(fā)現(xiàn)了一個(gè)新細(xì)節(jié)，而壓力正是通過這個(gè)途徑來產(chǎn)生副作用的。他們發(fā)現(xiàn)，影響學(xué)習(xí)和記憶的并不是由人們熟知的遍布全身的激素皮質(zhì)醇造成的，而是強(qiáng)大的壓力激發(fā)了一部分分子（促腎上腺皮質(zhì)激素），由它所釋放的荷爾蒙擾亂了大腦收集、儲(chǔ)存信息的過程。

當(dāng)神經(jīng)元的突觸（兩個(gè)神經(jīng)元之間或神經(jīng)元與效應(yīng)器細(xì)胞之間相互接觸、并借以傳遞信息的部位）傳遞信息時(shí)，人們才能進(jìn)行學(xué)習(xí)和記憶。這些突觸存在于神經(jīng)元的突出（樹突刺）這樣的特殊神經(jīng)元分支上。

在鼠科動(dòng)物試驗(yàn)中，Baram研究組發(fā)現(xiàn)海馬體（大腦皮質(zhì)的一個(gè)內(nèi)褶區(qū)，進(jìn)行學(xué)習(xí)和記憶的地方）中促腎上腺皮質(zhì)激素的釋放迅速破壞了樹突刺，這樣便影響了突觸對(duì)信息的收集和儲(chǔ)存。

研究還發(fā)現(xiàn)，用促腎上腺皮質(zhì)激素受體分子阻止激素之間的相互作用可以消除壓力對(duì)海馬體細(xì)胞樹突刺的傷害。

除此之外，研究者們還通過注射少量的合成促腎上腺皮質(zhì)激素模擬壓力對(duì)樹突刺的影響，觀察樹突刺在幾分鐘內(nèi)收縮的狀況。Baram說：“幸運(yùn)的是，當(dāng)我們移除促腎上腺皮質(zhì)激素的時(shí)候，樹突刺又恢復(fù)了原來的樣子。”

Baram還提到他們正在研究一種物質(zhì)，它能阻止促腎上腺皮質(zhì)激素受體的運(yùn)作，而且這次研究為一種全新療法的發(fā)明奠定了良好的理論基礎(chǔ)。這種療法以正在研究的物質(zhì)為基礎(chǔ)，且能處理由壓力導(dǎo)致的學(xué)習(xí)及記憶損害的問題。

這篇報(bào)告刊登在3月12日《神經(jīng)科學(xué)雜志》上，加州大學(xué)歐文分校的Yuncai Chen, Celine Dubé 和 Courtney Burgdorff也參與了此次研究。此次研究由美國國立衛(wèi)生研究院贊助支持。