Neuron：长期的压力会损伤记忆力

曾经经历过长期压力的人会在自身的情绪和清晰思考能力方面产生负面影响，新的一项研究揭示了人类大脑神经中的一种新的机制，这种机制是重复压力可以损害人的记忆力，这项研究刊登在了国际神经学领域权威杂志Neuron上，而且这项研究也为为什么压力反应可以引起众多精神疾病提供了新的见解。

众所周知，应激激素可以影响额前叶皮质（PFC），PFC是大脑中的一块区域，可以控制大脑的高水平执行功能，比如工作记忆和决策的决定，“以前的研究表明，慢性的压力的可以损害PFC相关的行为，比如神经的灵活性和精神的注意力等，然而，对于压力引起的生理性后果和PFC中长期压力的分子靶点，尤其是在青春期大脑遇到过更多的压力时，williamhill asia 却知之甚少。”研究者表示。

研究者用幼鼠进行相关实验，观察是否重复的压力可以对谷氨酸受体有负面的影响，谷氨酸信号在PFC功能的正常发挥上扮演着重要的作用，结果表明，在面对重复压力时，幼鼠大脑中的谷氨酸受体明显减少，进而引起PFC相关的认知行为和活动的缺失，研究者识别出了压力引起谷氨酸受体减少的分子机制，并且表示，如果破坏这些分子机制的话，因为压力引起的谷氨酸受体水平的降低以及认知行为的缺失便会恢复。

研究者识别出的谷氨酸受体的缺失是重复压力和慢性压力导致的PFC功能异常的主要靶点因素，研究者最后表示，因为PFC的功能障碍可以引起多样性的压力相关的精神疾病，研究压力影响PFC的分子机制，对于williamhill asia 更清楚的了解压力在影响身心疾病中所扮演的角色方面至关重要。（生物谷T.Shen编译）

doi:10.1016/j.neuron.2011.12.033
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Repeated Stress Causes Cognitive Impairment by Suppressing Glutamate Receptor Expression and Function in Prefrontal Cortex

Eunice Y. Yuen1, 2, Jing Wei1, 2, Wenhua Liu1, Ping Zhong1, Xiangning Li1, Zhen Yan1,

Chronic stress could trigger maladaptive changes associated with stress-related mental disorders; however, the underlying mechanisms remain elusive. In this study, we found that exposing juvenile male rats to repeated stress significantly impaired the temporal order recognition memory, a cognitive process controlled by the prefrontal cortex (PFC). Concomitantly, significantly reduced AMPAR- and NMDAR-mediated synaptic transmission and glutamate receptor expression were found in PFC pyramidal neurons from repeatedly stressed animals. All these effects relied on activation of glucocorticoid receptors and the subsequent enhancement of ubiquitin/proteasome-mediated degradation of GluR1 and NR1 subunits, which was controlled by the E3 ubiquitin ligase Nedd4-1 and Fbx2, respectively. Inhibition of proteasomes or knockdown of Nedd4-1 and Fbx2 in PFC prevented the loss of glutamatergic responses and recognition memory in stressed animals. Our results suggest that repeated stress dampens PFC glutamatergic transmission by facilitating glutamate receptor turnover, which causes the detrimental effect on PFC-dependent cognitive processes.