根據(jù)UC Irvine研究發(fā)現(xiàn)：在發(fā)育過程中，決定腦細胞生長的一類蛋白對長時性記憶也有著至關(guān)重要的作用,。這些發(fā)現(xiàn)有助于更好多地理解和治療正常衰老和老年癡呆病人認知的衰退,。在PNAS雜志上有這些發(fā)現(xiàn)的在線版本,。
??“這項研究為發(fā)育過程中一種分子進程基本原理在成人中記憶和記憶模式的再循環(huán)提供了強有力的證據(jù)，”神經(jīng)行為生物學(xué)UCL系主任Thomas J. Carew, Donald Bren教授說,，“這為大腦里的分子規(guī)則在一生中是如何適應(yīng)不同的目的而重新使用的提供了一個驚人的例子,。”
??研究者證實，生長因子類蛋白對長時性記憶的誘導(dǎo)和對中樞神經(jīng)系統(tǒng)的發(fā)育具有同等重要性,。象大腦衍生滋養(yǎng)因子（BDNF）等生長因子通過特異受體,，如TrkB，象鑰匙和鎖一樣結(jié)合于腦細胞,。研究者使用“分子策略”保存結(jié)合在合適TrkB受體蛋白的實驗策略來決定BDNF類生長因子在記憶形成中的重要性,。
??由于海產(chǎn)蝸牛有比較大的腦細胞，科學(xué)家常常用Aplysia蝸牛來作為學(xué)習(xí)和記憶的研究材料,。Aplysia蝸牛接受到間隔15分鐘,，連續(xù)的5次尾部電震，電震過后數(shù)天和數(shù)周,，動物表現(xiàn)出很強的撤回反射,。
??當(dāng)Aplysia蝸牛受到電震時，從大腦釋放的5-羥色胺促進沖擊相關(guān)的長時性記憶,。然而,，當(dāng)阻斷BDNF類生長因子和TrkB受體的交互關(guān)系時， Carew和他的同事發(fā)現(xiàn),，僅僅5-羥色胺不足以保存電震引起的長時性記憶,。當(dāng)短時記憶被保存時，蝸牛通常記得24小時內(nèi),，也就是前一天發(fā)生的事-----,，蝸牛對電震沒有記憶。Carew及其同事進一步研究表明,，當(dāng)阻止生長因子的行為時,，阻斷電震處理會誘導(dǎo)反射回路中腦細胞之間聯(lián)接的長期增強。
??“我們不會期望：響應(yīng)5-羥色胺而分泌的生長因子對于長時記憶的形成是至關(guān)重要的,，”Carew說,，“但很明顯，沒有這些生長因子,，長時記憶的形成就沒法發(fā)生,。”
??Carew的發(fā)現(xiàn)為失憶癥的治療打開了大門。“這為我們干涉治療提供了強有力的線索,，如果我們知道生長因子對長時記憶是重要的,，那么我們可以研究老年癡呆癥等疾病的補救治療,。
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.
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