根据UC Irvine研究发现：在发育过程中，决定脑细胞生长的一类蛋白对长时性记忆也有着至关重要的作用。这些发现有助于更好多地理解和治疗正常衰老和老年痴呆病人认知的衰退。在PNAS杂志上有这些发现的在线版本。
??“这项研究为发育过程中一种分子进程基本原理在成人中记忆和记忆模式的再循环提供了强有力的证据，”神经行为生物学UCL系主任Thomas J. Carew, Donald Bren教授说，“这为大脑里的分子规则在一生中是如何适应不同的目的而重新使用的提供了一个惊人的例子。”
??研究者证实，生长因子类蛋白对长时性记忆的诱导和对中枢神经系统的发育具有同等重要性。象大脑衍生滋养因子（BDNF）等生长因子通过特异受体，如TrkB，象钥匙和锁一样结合于脑细胞。研究者使用“分子策略”保存结合在合适TrkB受体蛋白的实验策略来决定BDNF类生长因子在记忆形成中的重要性。
??由于海产蜗牛有比较大的脑细胞，科学家常常用Aplysia蜗牛来作为学习和记忆的研究材料。Aplysia蜗牛接受到间隔15分钟，连续的5次尾部电震，电震过后数天和数周，动物表现出很强的撤回反射。
??当Aplysia蜗牛受到电震时，从大脑释放的5-羟色胺促进冲击相关的长时性记忆。然而，当阻断BDNF类生长因子和TrkB受体的交互关系时， Carew和他的同事发现，仅仅5-羟色胺不足以保存电震引起的长时性记忆。当短时记忆被保存时，蜗牛通常记得24小时内，也就是前一天发生的事-----，蜗牛对电震没有记忆。Carew及其同事进一步研究表明，当阻止生长因子的行为时，阻断电震处理会诱导反射回路中脑细胞之间联接的长期增强。
??“我们不会期望：响应5-羟色胺而分泌的生长因子对于长时记忆的形成是至关重要的，”Carew说，“但很明显，没有这些生长因子，长时记忆的形成就没法发生。”
??Carew的发现为失忆症的治疗打开了大门。“这为我们干涉治疗提供了强有力的线索，如果我们知道生长因子对长时记忆是重要的，那么我们可以研究老年痴呆症等疾病的补救治疗。
英文原文：
Proteins necessary for brain development found to be critical for long-term memory
Importance of growth factors in memory formation could aid development of strategies against cognitive decline
Irvine, Calif., September 5, 2006 - A type of protein crucial for the growth of brain cells during development appears to be equally important for the formation of long-term memories, according to researchers at UC Irvine. The findings could lead to a better understanding of, and treatments for, cognitive decline associated with normal aging and diseases such as Alzheimer’s.
The findings appear in the early online edition of the Proceedings of the National Academy of Sciences.
“This study presents strong evidence that a molecular process fundamental during development is retained in the adult and recycled in the service of memory formation,” said Thomas J. Carew, Donald Bren Professor and chair of UCI’s Department of Neurobiology and Behavior. “It is a striking example of how molecular rules employed in building a brain are often reused for different purposes throughout a lifetime.”
The researchers have shown that proteins known as growth factors are as essential for the induction of long-term memory as they are for the development of the central nervous system. These growth factors, such as brain derived neurotrophic factor (BDNF), bind onto the brain cell through a specific type of receptor known as TrkB, much the same way a key fits into a lock. As an experimental strategy to determine the importance of BDNF-like growth factors in forming memories, the researchers used a “molecular trick” to keep the proteins from binding with the appropriate TrkB receptors.
For the experiment, the scientists used wild-caught Aplysia, a marine snail frequently studied in learning and memory because of its large brain cells. The Aplysia received a series of five tail shocks, spaced 15 minutes apart. The shocks cause the animals to exhibit heightened withdrawal reflexes days and weeks after the shocks are over.
When the animals are shocked, a brain chemical known as serotonin is released that promotes the formation of a long-term memory associated with the shocks. However, when Carew and his colleagues blocked the interaction between the BDNF-like growth factors and the TrkB receptors, they found that serotonin alone was not enough to retain the long-term memory of the shock. While short-term memory was retained, 24 hours later the snails – which normally would remember the events of the previous day – exhibited no memory of the shocks. Carew and colleagues went on to show that, when the actions of the growth factors were prevented, long-term enhancement of the connections between the brain cells in the reflex circuit normally induced by the shock treatment was also blocked.
“We would never have expected that the secretion of these growth factors in response to serotonin would be critical for long-term memory formation in this system,” Carew said. “But it is apparent that without them, this process cannot happen.”
According to Carew, these findings could open possible avenues for treatments relating to memory loss. “This gives us some strong clues as to what we should be looking into for therapeutic interventions,” he said. “If we know that growth factors are important for long-term memory, then we can look at possible remedial roles they might play in diseases such as Alzheimer’s and dementia.”
Carew is a pioneer in the field known as the cellular biology of learning, which combines the disciplines of psychology and neurobiology. He held an endowed chair at Yale before coming to UCI in 2000. In 2001 he was elected a fellow of the American Association for the Advancement of Science and was named a fellow of the American Academy of Arts and Sciences in 2004.
Shiv Sharma of the National Brain Research Center in India; and Carolyn Sherff, Shara Stough and Vickie Hsuan of UCI collaborated with Carew on the study, which was funded by the National Institute of Mental Health.
About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students and about 1,400 faculty members. The second-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3.3 billion. For more UCI news, visit www.today.uci.edu.
