加利福尼大学欧文分校的研究人员发现,持续几个小时的短时间压力就可以损害大脑中与学习和记忆有关区域脑细胞的沟通。
据每日科学报道,以往人们知道,持续几周或几个月的严重压力可损伤大脑学习和记忆区域中细胞的通信交流,但这次研究首次提出了短时间压力会产生相似影响的证据。
“压力在我们生活中常见,不可避免。” 加利福尼大学欧文医学院神经学主任泰利Z.巴拉姆博士说。“我们这一发现为当前开发预防这种不良影响的药物起到重要作用,也有助于了解为什么有些人在压力状态下健忘或者很难记住一些事情。”
在这项研究中,巴拉姆和同事发现了压力产生这种作用的一个新的途径。他们发现,与其说是压力激素皮质醇产生了这种作用,倒不如说是巨大的压力激活了促肾上腺素释放激素(CRH)破坏了大脑的连接和储存记忆的过程。
学习和记忆与突触有关。脑细胞通过突触进行通信交流。这些突触呈特殊的枝状突起在神经元上,称作树突棘。
在对小鼠的研究中发现,大脑中的主要学习和记忆中枢海马释放CRH导致了这些树突棘的快速蜕变,从而削弱了突触的结合力和储存记忆的能力。
研究发现,抑制CRH与受体的相互作用就可以消除压力对海马细胞中与学习和记忆有关的树突棘的损害。
此外,研究人员用低剂量的合成CRH替换压力对树突棘的作用,观察树突棘的恢复情况。“一旦去掉CRH,树突棘似乎又恢复了原来情况。”巴拉姆说。
巴拉姆还说,有一些可以抑制CRH受体的药物正在开发中,这项研究将在把这些药物用于压力相关的学习和记忆力丧失的治疗上发挥重要作用。
这项研究发表在3月12日出版的《神经学杂志》(The Journal of Neuroscience)上。(来源:中国公众科技网)
生物谷推荐原始出处:
(The Journal of Neuroscience),28(11):2903-2911,Yuncai Chen,Tallie Z. Baram
Rapid Loss of Dendritic Spines after Stress Involves Derangement of Spine Dynamics by Corticotropin-Releasing Hormone
Yuncai Chen,1 Céline M. Dubé,1 Courtney J. Rice,2 and Tallie Z. Baram1,2
Departments of 1Pediatrics and 2Anatomy/Neurobiology, University of California Irvine, Irvine, California 92697-4475
Correspondence should be addressed to Dr. Tallie Z. Baram, Departments of Pediatrics and Anatomy/Neurobiology, University of California Irvine, Medical Sciences I, ZOT: 4475, Irvine, CA 92697-4475. Email: tallie@uci.edu
Chronic stress causes dendritic regression and loss of dendritic spines in hippocampal neurons that is accompanied by deficits in synaptic plasticity and memory. However, the responsible mechanisms remain unresolved. Here, we found that within hours of the onset of stress, the density of dendritic spines declined in vulnerable dendritic domains. This rapid, stress-induced spine loss was abolished by blocking the receptor (CRFR1) of corticotropin-releasing hormone (CRH), a hippocampal neuropeptide released during stress. Exposure to CRH provoked spine loss and dendritic regression in hippocampal organotypic cultures, and selective blockade of the CRFR1 receptor had the opposite effect. Live, time-lapse imaging revealed that CRH reduced spine density by altering dendritic spine dynamics: the peptide selectively and reversibly accelerated spine retraction, and this mechanism involved destabilization of spine F-actin. In addition, mice lacking the CRFR1 receptor had augmented spine density. These findings support a mechanistic role for CRH–CRFR1 signaling in stress-evoked spine loss and dendritic remodeling.