加拿大麦吉尔大学分子生物学家纳胡姆·索伯格教授带领的研究小组，发现一种特定基因突变的实验室老鼠，其学习和记忆的能力相比于一般正常老鼠有明显的提高。科学家期望，基于这个发现，可以研发出治疗老年痴呆病等痴呆病症的药物。研究文章刊载于4月6日出版的《细胞》杂志上。
研究人员在实验中比较了基因突变老鼠和正常老鼠在一系列标准实验中的表现，特别是在水迷宫试验中，基因突变鼠比正常鼠的学习记忆能力提高了一倍，这种不明基因通常会提高一种自然记忆堵塞蛋白的水平。研究人员认为，在那些发生基因变化的老鼠中，这种起抑制作用的蛋白产生得较少，导致老鼠学得更快，记忆时间更长。
研究人员表示，他们的工作就是使老鼠发生基因突变，这个突变的基因生产一种蛋白，这种蛋白可以控制在细胞内生成其它蛋白的速度。当突变基因产生后，对学习和记忆有抑制作用的蛋白数量产生得就少了。
索伯格表示，下一步工作将是寻找一种可以促使基因发生突变的化合物，也许这种化合物就是可以提高记忆的药物。如果能够找到这种化合物，也许就有机会为治疗老年痴呆等病症找到一种新的途径。也许这种药物无法治疗疾病本身，但至少可以帮助缓解疾病的症状。
部分英文原文：
Cell
Volume 129, Issue 1 , 6 April 2007, Pages 195-206
eIF2α Phosphorylation Bidirectionally Regulates the Switch from Short- to Long-Term Synaptic Plasticity and Memory
Mauro Costa-Mattioli1, , , Delphine Gobert6, Elad Stern7, Karine Gamache2, Rodney Colina1, Claudio Cuello3, Wayne Sossin4, Randal Kaufman8, Jerry Pelletier1, Kobi Rosenblum7, Krešimir Krnjević5, Jean-Claude Lacaille6, Karim Nader2 and Nahum Sonenberg1, ,
1Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
2Department of Psychology, McGill University, Montreal, Quebec, H3G 1Y6, Canada
3Department of Pharmacology, McGill University, Montreal, Quebec, H3G 1Y6, Canada
4Departments of Neurology and Neurosurgery, McGill University, Montreal, Quebec, H3G 1Y6, Canada
5Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada
6Département de Physiologie, Université de Montréal, Montréal, Québec, H3C 3J7, Canada
7Center for Brain and Behavior, University of Haifa, Haifa, 30905, Israel
8Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, 49109-0650, USA
Received 9 July 2006; revised 4 December 2006; accepted 29 January 2007. Published: April 5, 2007. Available online 5 April 2007.
Summary
The late phase of long-term potentiation (LTP) and memory (LTM) requires new gene expression, but the molecular mechanisms that underlie these processes are not fully understood. Phosphorylation of eIF2α inhibits general translation but selectively stimulates translation of ATF4, a repressor of CREB-mediated late-LTP (L-LTP) and LTM. We used a pharmacogenetic bidirectional approach to examine the role of eIF2α phosphorylation in synaptic plasticity and behavioral learning. We show that in eIF2α+/S51A mice, in which eIF2α phosphorylation is reduced, the threshold for eliciting L-LTP in hippocampal slices is lowered, and memory is enhanced. In contrast, only early-LTP is evoked by repeated tetanic stimulation and LTM is impaired, when eIF2α phosphorylation is increased by injecting into the hippocampus a small molecule, Sal003, which prevents the dephosphorylation of eIF2α. These findings highlight the importance of a single phosphorylation site in eIF2α as a key regulator of L-LTP and LTM formation.
Author Keywords: MOLNEURO; RNA; SYSNEURO
