2012年9月15日 訊 /生物谷BIOON/ --在兒童時(shí)期自閉癥患者的大腦就會(huì)出現(xiàn)一些廣泛性發(fā)育障礙（pervasive developmental disorder），瑞士巴塞爾大學(xué)的Peter Scheiffele和Kaspar Vogt教授近日在自閉癥患者的大腦中發(fā)現(xiàn)并扭轉(zhuǎn)了一個(gè)特定功能障礙的神經(jīng)回路,。這是一個(gè)有助于開(kāi)發(fā)自閉癥藥物的研究,，相關(guān)論文發(fā)表在Science雜志上。
據(jù)統(tǒng)計(jì),，大約百分之一的兒童可發(fā)生可歸類為自閉癥的障礙,。自閉癥是一種遺傳性的大腦發(fā)育障礙疾病目前，目前尚無(wú)法治愈,，行為治療等也僅可緩解一些癥狀,。已經(jīng)發(fā)現(xiàn)自閉癥患者有超過(guò)300個(gè)基因發(fā)生突變，其中包括神經(jīng)連接蛋白-3（neuroligin-3）,它與突觸的形成有關(guān),。
neuroligin-3基因缺失的小鼠表現(xiàn)出自閉癥的一些癥狀,。通過(guò)與羅氏合作，研究者發(fā)現(xiàn),，調(diào)節(jié)神經(jīng)元之間信號(hào)傳導(dǎo)的谷氨酸受體表達(dá)上升,，導(dǎo)致了突觸信號(hào)傳導(dǎo)的異常，進(jìn)而干擾了神經(jīng)元回路的功能和可塑性,，長(zhǎng)此以往大腦的發(fā)育和功能受到影響,。
若刺激neuroligin-3基因缺失小鼠neuroligin-3的表達(dá)，谷氨酸受體的表達(dá)便會(huì)降到正常水平,，自閉癥患者大腦中的缺陷結(jié)構(gòu)也隨之消失,。因此，這些谷氨酸受體可以作為自閉癥治療的靶點(diǎn),，此項(xiàng)研究的科學(xué)家正和羅氏合作開(kāi)發(fā)谷氨酸受體的拮抗劑,。（生物谷Bioon.com）
編譯自Scientists reverse disorder of neuronal circuits in autism
doi:10.1126/science.1224159
PMC:
PMID:
Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism
Stéphane J. Baudouin1, Julien Gaudias1, Stefan Gerharz1,*, Laetitia Hatstatt1, Kuikui Zhou2, Pradeep Punnakkal1, Kenji F. Tanaka3,4, Will Spooren5, Rene Hen3, Chris I. De Zeeuw2,6, Kaspar Vogt1, Peter Scheiffele
The genetic heterogeneity of autism poses a major challenge for identifying mechanism-based treatments. A number of rare mutations are associated with autism, and it is unclear whether these result in common neuronal alterations. Monogenic syndromes, such as fragile X, include autism as one of their multifaceted symptoms and have revealed specific defects in synaptic plasticity. We discovered an unexpected convergence of synaptic pathophysiology in a nonsyndromic form of autism with those in fragile X syndrome. Neuroligin-3 knockout mice (a model for nonsyndromic autism) exhibited disrupted hetero-synaptic competition and perturbed metabotropic glutamate receptor-dependent synaptic plasticity, a hallmark of fragile X. These phenotypes could be rescued by re-expression of neuroligin-3 in juvenile mice, highlighting the possibility for reverting neuronal circuit alterations in autism after completion of development.
