学习记忆易受创，短期压力勿小觑

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.

加州大学欧文分校研究人员发现，即使只是几小时的短期压力也扰乱脑细胞间的正常运作，而这些运作正关系到学习和记忆。

我们知道，持续长达几周甚至几个月的强大压力会对大脑学习和记忆区域的神经细胞传导造成损害。但是这次实验第一次发现，短期压力也会产生同样的破坏力。

加州大学欧文分校医学院神经科学Danette Shepard 主席，这次研究的领导者，Tallie Z. Baram博士说道：“我们的生活中到处都存在着压力，躲也躲不了。我们这次的研究成果将起到非常重要的作用。根据这些研究成果，我们可以制造新的药物以减轻不良影响，并且深入探究有些人为什么在压力下容易健忘或者记忆力出现问题。”

在这次研究中，Baram及他的同事还发现了一个新细节，而压力正是通过这个途径来产生副作用的。他们发现，影响学习和记忆的并不是由人们熟知的遍布全身的激素皮质醇造成的，而是强大的压力激发了一部分分子（促肾上腺皮质激素），由它所释放的荷尔蒙扰乱了大脑收集、储存信息的过程。

当神经元的突触（两个神经元之间或神经元与效应器细胞之间相互接触、并借以传递信息的部位）传递信息时，人们才能进行学习和记忆。这些突触存在于神经元的突出（树突刺）这样的特殊神经元分支上。

在鼠科动物试验中，Baram研究组发现海马体（大脑皮质的一个内褶区，进行学习和记忆的地方）中促肾上腺皮质激素的释放迅速破坏了树突刺，这样便影响了突触对信息的收集和储存。

研究还发现，用促肾上腺皮质激素受体分子阻止激素之间的相互作用可以消除压力对海马体细胞树突刺的伤害。

除此之外，研究者们还通过注射少量的合成促肾上腺皮质激素模拟压力对树突刺的影响，观察树突刺在几分钟内收缩的状况。Baram说：“幸运的是，当我们移除促肾上腺皮质激素的时候，树突刺又恢复了原来的样子。”

Baram还提到他们正在研究一种物质，它能阻止促肾上腺皮质激素受体的运作，而且这次研究为一种全新疗法的发明奠定了良好的理论基础。这种疗法以正在研究的物质为基础，且能处理由压力导致的学习及记忆损害的问题。

这篇报告刊登在3月12日《神经科学杂志》上，加州大学欧文分校的Yuncai Chen, Celine Dubé 和 Courtney Burgdorff也参与了此次研究。此次研究由美国国立卫生研究院赞助支持。