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【medical-news】酶可以改变长期记忆

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NIH Research Matters

March 14, 2011

Enzyme Can Alter Long-Term Memories
Even long after memories have formed, they can be enhanced or erased by altering the activity of a single brain enzyme, a new study reveals. The finding may give insight into potential strategies for treating a variety of memory disorders.

A neuron in a rat brain's cortex over-expressing PKMzeta (blue). Source: Dr. Todd Sacktor, SUNY Downstate Medical Center.
Researchers have made significant advances in enhancing or disrupting memories, but these generally involve manipulations during short windows of time just after learning or upon retrieval of a memory. Memories seem to be temporarily fragile and changeable during these time-limited windows. But until recently, no method has been shown to affect memories formed outside these windows, such as ones from the distant past.

Scientists previously showed that a brain enzyme called PKMzeta is critical for the integrity of previously established memories. In animal models, the enzyme seems to play a central role in maintaining the integrity of long-term memories induced using a variety of well-established behavioral learning methods.

In their latest study, the team—led by Dr. Todd Sacktor of the SUNY Downstate Medical Center in New York City and Dr. Yadin Dudai of the Weizmann Institute of Science in Rehovot, Israel—further explored the effects of manipulating PKMzeta levels in the brain. Their work was partly supported by NIH’s National Institute of Mental Health (NIMH).

The researchers paired genetic engineering with a model called conditioned taste aversion that they had used in their previous work. Rats were taught to associate a nauseating sensation with saccharin and so to shun the sweet taste. Seven days after the animals were trained, the researchers used a virus to overexpress either PKMzeta or a mutant inactive form of the enzyme. The scientists infused these viruses into the insular cortex, a part of the brain that their previous work had shown was critical for the taste aversion memory. The results appeared in Science on March 4, 2011.

Overexpression of PKMzeta, the researchers found, significantly enhanced taste aversion memories. This was true of memories that had already been formed as well as memories formed after the transgene was infused. When the researchers trained the rats to shun 2 different tastes at different times, PKMzeta overexpression enhanced the long-term memory of both. Expression of the inactive form of PKMzeta, in contrast, erased the memories—much as a chemical blocker had in their previous study.

"Our study is the first to demonstrate that, in the context of a functioning brain in a behaving animal, a single molecule, PKMzeta, is both necessary and sufficient for maintaining long-term memory," says Sacktor.

This approach affects multiple memories stored in the targeted brain area. Further work will be needed to understand how to home in on specific memories to treat conditions such as post-traumatic stress disorder. The discovery could also point the way toward new types of memory enhancers for treating amnesia or cognitive decline.

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NIH Research Matters
NIH研究项目

March 14, 2011
2011年3月14日

Enzyme Can Alter Long-Term Memories
一种可以改变长期记忆的酶
Even long after memories have formed, they can be enhanced or erased by altering the activity of a single brain enzyme, a new study reveals. The finding may give insight into potential strategies for treating a variety of memory disorders.
一项新的研究显示，即使在记忆形成很长时间以后，只要改变大脑中一种酶的活性，就可以来促进或消除这些记忆。这些发现可以指导针对一系列记忆紊乱疾病的治疗策略的开发。

A neuron in a rat brain's cortex over-expressing PKMzeta (blue).Source: Dr. Todd Sacktor, SUNY Downstate Medical Center.
大鼠大脑皮质过度表达PKMzeta蛋白（蓝色部分）的神经元。来源：纽约州立大学下城医学中心Todd Sacktor博士
Researchers have made significant advances in enhancing or disrupting memories, but these generally involve manipulations during short windows of time just after learning or upon retrieval of a memory. Memories seem to be temporarily fragile and changeable during these time-limited windows. But until recently, no method has been shown to affect memories formed outside these windows, such as ones from the distant past.
在此之前，研究人员已经在记忆的促进和消除方面取得了显著的进步，但是这些研究都只是在记忆学习或提取后很短的时间窗内进行的。在这个时间窗内，记忆似乎是暂时性脆弱和可变的。直到最近，研究人员才找到了如何来改变在这个时间窗外形成的记忆（即较早以前形成的记忆）的方法。

Scientists previously showed that a brain enzyme called PKMzeta is critical for the integrity of previously established memories. In animal models, the enzyme seems to play a central role in maintaining the integrity of long-term memories induced using a variety of well-established behavioral learning methods.
此前有研究发现大脑中一种叫PKMzeta的酶对于维持以往形成记忆的完整性十分重要。动物模型的研究表明这种酶在维持以往通过一系列公认行为学习得到的记忆的完整性方面起着核心的作用。

In their latest study, the team—led by Dr. Todd Sacktor of the SUNY Downstate Medical Center in New York City and Dr. Yadin Dudai of the Weizmann Institute of Science in Rehovot, Israel—further explored the effects of manipulating PKMzeta levels in the brain. Their work was partly supported by NIH’s National Institute of Mental Health (NIMH).
在最新的一项研究中，由纽约州立大学下城医学中心（纽约）Todd Sacktor博士和魏兹曼科学中心（以色列雷霍沃特）Yadin Dudai博士领衔的团队进一步揭示了改变大脑中PKMzeta酶水平对记忆的影响。这项研究得到了NIH所属国家精神卫生研究所（NIMH）的部分资助。

The researchers paired genetic engineering with a model called conditioned taste aversion that they had used in their previous work. Rats were taught to associate a nauseating sensation with saccharin and so to shun the sweet taste. Seven days after the animals were trained, the researchers used a virus to overexpress either PKMzeta or a mutant inactive form of the enzyme. The scientists infused these viruses into the insular cortex, a part of the brain that their previous work had shown was critical for the taste aversion memory. The results appeared in Science on March 4, 2011.
在这项研究中，研究人员结合采用了基因工程方法和以往研究中采用的条件性厌味模型。通过训练使大鼠建立起糖精和恶心感的相关性，并对甜味产生排斥。这样训练7天以后，研究人员采用一种病毒来过度表达这种酶活性或突变失活形态。然后将这类病毒导入大脑内岛状皮质，以往发现这块区域在厌味记忆中起着重要作用的区域之一。这项研究的结果发表在2011年3月4日出版的科学杂志上。

Overexpression of PKMzeta, the researchers found, significantly enhanced taste aversion memories. This was true of memories that had already been formed as well as memories formed after the transgene was infused. When the researchers trained the rats to shun 2 different tastes at different times, PKMzeta overexpression enhanced the long-term memory of both. Expression of the inactive form of PKMzeta, in contrast, erased the memories—much as a chemical blocker had in their previous study.
研究人员发现，无论是针对以往已经形成的记忆还是注入转基因后形成的记忆，PKMzeta过度表达都可以显著得促进大鼠的厌味记忆。当研究人员在不同的时间训练大鼠对两种不同的味道产生厌恶，PKMzeta过度表达可以对这两种长期厌恶记忆都有促进作用。相反的，如果表达了PKMzeta的失活形式，就像以往试验中曾采用的化学性阻断剂一样，可以消除形成的记忆。

"Our study is the first to demonstrate that, in the context of a functioning brain in a behaving animal, a single molecule, PKMzeta, is both necessary and sufficient for maintaining long-term memory," says Sacktor.
Sacktor博士说：“我们的试验首次证实了在行为学试验动物的功能性大脑皮层存在的一种单分子酶，PKMzeta，对于维持长期记忆是必要而且是充分的。”

This approach affects multiple memories stored in the targeted brain area. Further work will be needed to understand how tohome inon specific memories to treat conditions such as post-traumatic stress disorder. The discovery could also point the way toward new types of memory enhancers for treating amnesia or cognitive decline.
这种方法可以改变储存在大脑特定领域的多种记忆。将来还需要进一步的研究，来发现如何恢复或找回某些特定的记忆，这样就可以用于对创伤后压力障碍症进行治疗。这项发现也会对治疗老年痴呆症或认知功能下降等疾病新类型药物的开发提供了一个方向。

整理后为（共944中文字）：

NIH研究项目

2011年3月14日

一种可以改变长期记忆的酶

一项新的研究显示，即使在记忆形成很长时间以后，只要改变大脑中一种酶的活性，就可以来促进或消除这些记忆。这些发现可以指导针对一系列记忆紊乱疾病的治疗策略的开发。

大鼠大脑皮质过度表达PKMzeta蛋白（蓝色部分）的神经元。来源：纽约州立大学下城医学中心Todd Sacktor博士
在此之前，研究人员已经在记忆的促进和消除方面取得了显著的进步，但是这些研究都只是在记忆学习或提取后很短的时间窗内进行的。在这个时间窗内，记忆似乎是暂时性脆弱和可变的。直到最近，研究人员才找到了如何来改变在这个时间窗外形成的记忆（即较早以前形成的记忆）的方法。

此前有研究发现大脑中一种叫PKMzeta的酶对于维持以往形成记忆的完整性十分重要。动物模型的研究表明这种酶在维持以往通过一系列公认行为学习得到的记忆的完整性方面起着核心的作用。

在最新的一项研究中，由纽约州立大学下城医学中心（纽约）Todd Sacktor博士和魏兹曼科学中心（以色列雷霍沃特）Yadin Dudai博士领衔的团队进一步揭示了改变大脑中PKMzeta酶水平对记忆的影响。这项研究得到了NIH所属国家精神卫生研究所（NIMH）的部分资助。

在这项研究中，研究人员结合采用了基因工程方法和以往研究中采用的条件性厌味模型。通过训练使大鼠建立起糖精和恶心感的相关性，并对甜味产生排斥。这样训练7天以后，研究人员采用一种病毒来过度表达这种酶活性或突变失活形态。然后将这类病毒导入大脑内岛状皮质，以往发现这块区域在厌味记忆中起着重要作用的区域之一。这项研究的结果发表在2011年3月4日出版的科学杂志上。

研究人员发现，无论是针对以往已经形成的记忆还是注入转基因后形成的记忆，PKMzeta过度表达都可以显著得促进大鼠的厌味记忆。当研究人员在不同的时间训练大鼠对两种不同的味道产生厌恶，PKMzeta过度表达可以对这两种长期厌恶记忆都有促进作用。相反的，如果表达了PKMzeta的失活形式，就像以往试验中曾采用的化学性阻断剂一样，可以消除形成的记忆。

Sacktor博士说：“我们的试验首次证实了在行为学试验动物的功能性大脑皮层存在的一种单分子酶，PKMzeta，对于维持长期记忆是必要而且是充分的。”

这种方法可以改变储存在大脑特定领域的多种记忆。将来还需要进一步的研究，来发现如何恢复或找回某些特定的记忆，这样就可以用于对创伤后压力障碍症进行治疗。这项发现也会对治疗老年痴呆症或认知功能下降等疾病新类型药物的开发提供了一个方向。

2011-03-28 11:06

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qjluo 编辑于 2011-03-29 07:29

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