日前,，法國(guó)和德國(guó)研究人員通過(guò)動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),，一種特定基因變異后,，會(huì)導(dǎo)致大腦某些區(qū)域連接神經(jīng)元的神經(jīng)突觸數(shù)量減少,，從而引發(fā)自閉癥。該研究結(jié)果有助于更好地了解與自閉癥相關(guān)的神經(jīng)生物學(xué)機(jī)制,。相關(guān)研究報(bào)告已刊登在最新一期的英國(guó)Nature雜志上,。
以往的研究已發(fā)現(xiàn)100多種基因的變異與自閉癥形成有關(guān)聯(lián)，但對(duì)它們扮演的確切角色和影響大小仍知之甚少,。法國(guó)巴斯德研究所和德國(guó)烏爾姆大學(xué)等機(jī)構(gòu)研究人員利用小鼠進(jìn)行研究發(fā)現(xiàn),，名為SHANK2的基因變異后,，小鼠擁有的大腦神經(jīng)突觸數(shù)量比正常小鼠少。SHANK2變異后,，小鼠并沒(méi)有表現(xiàn)出明顯生理和記憶問(wèn)題,，但它們比正常小鼠更為焦躁。此外,，這些小鼠還表現(xiàn)出社交問(wèn)題,，其大腦超聲波發(fā)聲的次數(shù)也減少了。
研究人員說(shuō),，小鼠的行為和大腦檢測(cè)數(shù)據(jù)都表明,，其患上了自閉癥。它們的研究成就在于從神經(jīng)生物學(xué)角度弄清了SHANK2如何讓小鼠產(chǎn)生自閉癥,。（生物谷Bioon.com）
doi:10.1038/nature11015
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Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2
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.
