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腾讯登录Nature：自闭症研究获进展
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日前，法国和德国研究人员通过动物实验发现，一种特定基因变异后，会导致大脑某些区域连接神经元的神经突触数量减少，从而引发自闭症。该研究结果有助于更好地了解与自闭症相关的神经生物学机制。相关研究报告已刊登在最新一期的英国<em>Nature</em>杂志上。
<!--more-->以往的研究已发现100多种基因的变异与自闭症形成有关联，但对它们扮演的确切角色和影响大小仍知之甚少。法国巴斯德研究所和德国乌尔姆大学等机构研究人员利用小鼠进行研究发现，名为SHANK2的基因变异后，小鼠拥有的大脑神经突触数量比正常小鼠少。SHANK2变异后，小鼠并没有表现出明显生理和记忆问题，但它们比正常小鼠更为焦躁。此外，这些小鼠还表现出社交问题，其大脑超声波发声的次数也减少了。
研究人员说，小鼠的行为和大脑检测数据都表明，其患上了自闭症。它们的研究成就在于从神经生物学角度弄清了SHANK2如何让小鼠产生自闭症。
<br/><strong>文献链接：</strong><br/>
<a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11015.html">http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11015.html</a>
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<br/><strong>Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2</strong><br/>
Michael J. Schmeisser, Elodie Ey, Stephanie Wegener,Juergen Bockmann, A. Vanessa Stempel,5 Angelika Kuebler, Anna-Lena Janssen, Patrick T. Udvardi, Ehab Shiban, Christina Spilker, Detlef Balschun, Boris V. Skryabin, Susanne tom Dieck, Karl-Heinz Smalla, Dirk Montag, Claire S. Leblond,Philippe Faure, Nicolas Torquet, Anne-Marie Le Sourd,Roberto Toro, Andreas M. Grabrucker, Sarah A. Shoichet, Dietmar Schmitz, Michael R. Kreutz, Thomas Bourgeron
Autism spectrum disorders comprise a range of neurodevelopmental disorders characterized by deficits in social interaction and communication, and by repetitive behaviour1. Mutations in synaptic proteins such as neuroligins2, 3, neurexins4, GKAPs/SAPAPs5 and ProSAPs/Shanks6, 7, 8, 9, 10 were identified in patients with autism spectrum disorder, but the causative mechanisms remain largely unknown. ProSAPs/Shanks build large homo- and heteromeric protein complexes at excitatory synapses and organize the complex protein machinery of the postsynaptic density in a laminar fashion11, 12. Here we demonstrate that genetic deletion of ProSAP1/Shank2 results in an early, brain-region-specific upregulation of ionotropic glutamate receptors at the synapse and increased levels of ProSAP2/Shank3. Moreover, ProSAP1/Shank2?/? mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced N-methyl-d-aspartate receptor-mediated excitatory currents at the physiological level. Mutants are extremely hyperactive and display profound autistic-like behavioural alterations including repetitive grooming as well as abnormalities in vocal and social behaviours. By comparing the data on ProSAP1/Shank2?/? mutants with ProSAP2/Shank3αβ?/? mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication. Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype.
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日前，法国和德国研究人员通过动物实验发现，一种特定基因变异后，会导致大脑某些区域连接神经元的神经突触数量减少，从而引发自闭症。该研究结果有助于更好地了解与自闭症相关的神经生物学机制。相关研究报告已刊登在最新一期的英国<em>Nature</em>杂志上。
<!--more-->以往的研究已发现100多种基因的变异与自闭症形成有关联，但对它们扮演的确切角色和影响大小仍知之甚少。法国巴斯德研究所和德国乌尔姆大学等机构研究人员利用小鼠进行研究发现，名为SHANK2的基因变异后，小鼠拥有的大脑神经突触数量比正常小鼠少。SHANK2变异后，小鼠并没有表现出明显生理和记忆问题，但它们比正常小鼠更为焦躁。此外，这些小鼠还表现出社交问题，其大脑超声波发声的次数也减少了。
研究人员说，小鼠的行为和大脑检测数据都表明，其患上了自闭症。它们的研究成就在于从神经生物学角度弄清了SHANK2如何让小鼠产生自闭症。
<br/><strong>文献链接：</strong><br/>
<a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11015.html">http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11015.html</a>
<div>
<br/><strong>Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2</strong><br/>
Michael J. Schmeisser, Elodie Ey, Stephanie Wegener,Juergen Bockmann, A. Vanessa Stempel,5 Angelika Kuebler, Anna-Lena Janssen, Patrick T. Udvardi, Ehab Shiban, Christina Spilker, Detlef Balschun, Boris V. Skryabin, Susanne tom Dieck, Karl-Heinz Smalla, Dirk Montag, Claire S. Leblond,Philippe Faure, Nicolas Torquet, Anne-Marie Le Sourd,Roberto Toro, Andreas M. Grabrucker, Sarah A. Shoichet, Dietmar Schmitz, Michael R. Kreutz, Thomas Bourgeron
Autism spectrum disorders comprise a range of neurodevelopmental disorders characterized by deficits in social interaction and communication, and by repetitive behaviour1. Mutations in synaptic proteins such as neuroligins2, 3, neurexins4, GKAPs/SAPAPs5 and ProSAPs/Shanks6, 7, 8, 9, 10 were identified in patients with autism spectrum disorder, but the causative mechanisms remain largely unknown. ProSAPs/Shanks build large homo- and heteromeric protein complexes at excitatory synapses and organize the complex protein machinery of the postsynaptic density in a laminar fashion11, 12. Here we demonstrate that genetic deletion of ProSAP1/Shank2 results in an early, brain-region-specific upregulation of ionotropic glutamate receptors at the synapse and increased levels of ProSAP2/Shank3. Moreover, ProSAP1/Shank2?/? mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced N-methyl-d-aspartate receptor-mediated excitatory currents at the physiological level. Mutants are extremely hyperactive and display profound autistic-like behavioural alterations including repetitive grooming as well as abnormalities in vocal and social behaviours. By comparing the data on ProSAP1/Shank2?/? mutants with ProSAP2/Shank3αβ?/? mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication. Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype.
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