Cell：研究人员发现能改善记忆的基因突变

From： Updated：2007-04-16

     加拿大研究人员2007年4月6日在科研期刊《细胞》上发表报告称，小鼠身上一种改变其思维的基因突变能使其长期记忆提高。研究人员认为，这些发现指出了可用于开发治疗记忆力减退的药物的一个潜在靶点。
    他们对一种基因进行了研究，通常这种基因能使一种天然记忆阻碍蛋白的浓度水平升高。携带有这种基因的一种缺陷版本的实验动物在经典的行为记忆试验中的表现得到了改善。而且，经作用相反的一种小分子物质处理后，最后记忆阻碍物的浓度会升高，实验动物出现了记忆力损害的迹象。 “能使记忆力增强的例子很少，尤其是通过删除基因的手段，”论文的作者，加拿大蒙特利尔的McGill大学的Nahum Sonenberg说。“在阐释记忆如何运作的大拼图中，这是一块小的拼图碎片，但很重要。”
    当调节蛋白eIF2α被经过化学改性，在它的氨基酸之一上加上一个磷酯基团，它即可将另一种因子的蛋白合成开关打开，这种因子能使记忆长期贮存所需要的基因停止生产。 Sonenberg 及其同事之前发现，缺乏进行进行磷酰化反应的酶的小鼠在某些训练条件下，记住新事物的能力很出色。研究人员们还指出，经过能增加eIF2α基因磷酰化反应的小分子物质处理的实验动物，在记忆试验中的表现会变差。这些数据表明，eIF2α基因磷酰化反应是对记忆实现双向控制的一个关键点，具有将长期记忆形成的开关打开或关闭的能力。
   “综合考虑，这些数据强烈支持这么一种看法，即在一些生理条件下，eIF2α基因磷酰化反应的减少是激活某种基因表达的一个关键组成步骤，这种基因表达能引起记忆形成所需的长期神经元突触变化,”研究人员们总结道。 “这些发现也引起了研究人员的兴趣，认为有这么种可能，即翻译调节因子可作为改善记忆的治疗靶点，比如说，用于治疗与记忆减退有关的各种人类异常。”

Figure 1. Late-LTP Is Induced by Single or Multiple Tetanic Trains in Hippocampal Slices from eIF2α^+/S51A Mice

(A) A single 100 Hz train of stimulation elicits only E-LTP in control slices (open circles), whereas LTP is sustained in eIF2α^+/S51A slices (closed circles; at 180 min, p < 0.01). The sustained L-LTP elicited in eIF2α^+/S51A slices is suppressed by (B) anisomycin (ANISO, closed circles; at 180 min p < 0.05) or (C) actinomycin-D (ACTD, closed circles; at 180 min p < 0.01). Horizontal bars indicate the period of incubation with anisomycin and actinomycin-D. (D) Similar L-LTP is induced by four tetanic trains in slices from WT and eIF2α^+/S51A mice (at 240 min p > 0.05). Data are means ± SEM; numbers of tests are indicated. Scale bar represents 5 ms, 100 μV.

原文出处：

April 6, 2007: 129 (1)

eIF2α Phosphorylation Bidirectionally Regulates the Switch from Short- to Long-Term Synaptic Plasticity and Memoryp195
Mauro Costa-Mattioli, Delphine Gobert, Elad Stern, Karine Gamache, Rodney Colina, Claudio Cuello, Wayne Sossin, Randal Kaufman, Jerry Pelletier, Kobi Rosenblum, Krešimir Krnjević, Jean-Claude Lacaille, Karim Nader, and Nahum Sonenberg
[Summary] [Full Text] [PDF] [Supplemental Data]

相关基因：

Eif2s1

Official Symbol: Eif2s1 and Name: eukaryotic translation initiation factor 2, subunit 1 alpha [Mus musculus]

Other Aliases: 0910001O23Rik, 2410026C18Rik, 35kDa, Eif2a, eIF2alpha

Other Designations: eukaryotic translation initiation factor 2A

Chromosome: 12; Location: 12 D1

GeneID: 13665

作者简介：

Nahum Sonenberg, Ph.D.

Nahum Sonenberg joined McGill University in 1979 and is currently James McGill Professor in the Department of Biochemistry and the McGill Cancer Centre. He received a Ph.D. in biochemistry at the Weizmann Institute of Science in Israel and joined the Roche Institute of Molecular Biology in the United States with a Chaim Weizmann postdoctoral fellowship. He is a CIHR Distinguished Scientist and has been a fellow of the Royal Society of Canada since 1992. In 2002, Dr. Sonenberg was awarded the Robert L. Noble Prize from the National Cancer Institute of Canada and, in 2005, the Killam Prize for Health Sciences. Dr. Sonenberg is an elected member of the American Academy of Arts and Sciences and the Royal Society of London.

RESEARCH ABSTRACT SUMMARY:

Nahum Sonenberg's primary research interest has been to understand the control of protein synthesis in eukaryotes. He investigates the importance of translational control in cancer, obesity, and learning and memory. He has also had a long-term interest in virology, and he studies poliovirus, rhinoviruses, HIV, and HCV. HHMI is currently funding his research on learning and memory.

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