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zoom RSS 脳内蛋白の欠如により自閉症が発症の可能性

<<   作成日時 : 2008/02/14 21:55   >>

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 自閉症が脳内の特定蛋白質の欠如で説明できるかもしれない。
画像 MITの研究者によれば、マウスを使った実験で、シナプス形成の鍵となる蛋白を遺伝的に欠くマウスは、空間記憶タスクの学習能力に優れているが、より早く忘れてしまうことがわかった。
 マウスで、Shank1 というシナプスの骨格となる蛋白を欠くと、シナプスの入力に反応する用意はできても長期記憶の維持ができない。
 自閉症スペクトラム(ASD)でShank3という蛋白の変異が関連している。
 時々、自閉症の人は信じられないような記憶力や音楽的な才能など目立ったスキルを持っている。ダスティンホフマンが映画「レインマン」中で演じた登場人物のような人は自閉症の学者と称される。
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Lack of Brain Protein May Explain 'Rain Man' Abilities
Autistic savants learn some tasks better, but forget faster, study suggests
-- Kevin McKeever
http://health.msn.com/health-topics/mental-health/articlepage.aspx?cp-documentid=100192860

Autistic savants learn some tasks better, but forget faster, study suggests.

TUESDAY, Feb. 12 (HealthDay News) -- The lack of a particular brain protein may explain the phenomenon of "Rain Man" -- autistic savants who learn some tasks better but also forget faster, say researchers at Massachusetts Institute of Technology.

Mice genetically engineered to lack a key protein used for building synapses -- the junctions through which brain cells communicate -- actually learned a spatial memory task faster and better than normal mice, according to findings in the Feb. 13 issue of the Journal of Neuroscience. But when tested weeks later, the altered mice couldn't remember what they had learned as well as normal mice, and they had trouble remembering contexts that should have provoked fear.

"These opposite effects on different types of learning are reminiscent of the mixed features of autistic patients, who may be disabled in some cognitive areas but show enhanced abilities in others," study co-author Albert Y. Hung, a staff neurologist at Massachusetts General Hospital, said in a prepared statement. "The superior learning ability of these mutant mice in a specific realm is reminiscent of human autistic savants."

The absence of this important synaptic scaffold protein, called Shank1, may "trap" the mice's synapses into a state in which the synapses are ready to respond to input but not maintain it in long-term memory, he said.

In humans, mutations in the closely related protein Shank3 have been linked to the autism spectrum of disorders (ASD) characterized by impaired social interaction, absent or delayed language development and repetitive behaviors. Occasionally, an autistic person has an outstanding skill, such as an incredible rote memory or musical ability. Such individuals, like the character Dustin Hoffman played in the film "Rain Man," may be referred to as autistic savants.

More information

The National Dissemination Center for Children with Disabilities has more about autism.

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The Journal of Neuroscience, February 13, 2008, 28(7):1697-1708; doi:10.1523/JNEUROSCI.3032-07.2008

Smaller Dendritic Spines, Weaker Synaptic Transmission, but Enhanced Spatial Learning in Mice Lacking Shank1

Albert Y. Hung,1,2 Kensuke Futai,1 Carlo Sala,3 Juli G. Valtschanoff,4 Jubin Ryu,1 Mollie A. Woodworth,1 Fleur L. Kidd,1 Clifford C. Sung,1 Tsuyoshi Miyakawa,5 Mark F. Bear,1 Richard J. Weinberg,4 and Morgan Sheng1

1The Picower Institute for Learning and Memory, The Institute of Physical and Chemical Research (RIKEN)-Massachusetts Institute of Technology Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, 2Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, 3Consiglio Nazionale delle Ricerche, Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Pharmacology, University of Milan, 20129 Milan, Italy, 4Department of Cell and Developmental Biology, and Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and 5Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan

Correspondence should be addressed to Morgan Sheng, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 46-4303, Cambridge, MA 02139. Email: msheng@mit.edu

Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, the Shank family of postsynaptic scaffold proteins are abundant and enriched in the postsynaptic density (PSD) of central excitatory synapses. When expressed in cultured hippocampal neurons, Shank promotes the maturation and enlargement of dendritic spines. Recently, Shank3 has been genetically implicated in human autism, suggesting an important role for Shank proteins in normal cognitive development. Here, we report the phenotype of Shank1 knock-out mice. Shank1 mutants showed altered PSD protein composition; reduced size of dendritic spines; smaller, thinner PSDs; and weaker basal synaptic transmission. Standard measures of synaptic plasticity were normal. Behaviorally, they had increased anxiety-related behavior and impaired contextual fear memory. Remarkably, Shank1-deficient mice displayed enhanced performance in a spatial learning task; however, their long-term memory retention in this task was impaired. These results affirm the importance of Shank1 for synapse structure and function in vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders.

Key words: postsynaptic density; gene knock-out; learning and memory; dendritic spine; autism; scaffolding proteins

Received July 4, 2007; revised Nov. 20, 2007; accepted Dec. 15, 2007.

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自閉症の症状の赤ちゃん
自閉症の症状の赤ちゃんというのはどのような赤ちゃんだと思いますか?自閉症の症状の赤ちゃんというのは人への関心を持つ気持ちがとても貧しかったり、集団行動になじめなかったりといった障害があります。自閉症の症状の赤ちゃんは大きくなるにつれて人へむける関心は難しくなって、人の動作を真似できないとか、教えても聞かないなどといった大きな症状に発展するといわれています。自閉症の症状の赤ちゃんの特徴としては、言葉が遅れていることと奇妙さがあることも特徴としてあげられます。他のお子さんよりも言... ...続きを見る
自閉症の赤ちゃんを持つ親のために・・・
2008/03/11 11:43

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