2012年11月5日 訊 /生物谷BIOON/ --近日，刊登于國(guó)際雜志The FASEB Journal上的一項(xiàng)研究發(fā)現(xiàn)或許為理解某些兒童的精神疾病帶來了革命性的進(jìn)展,，研究者發(fā)現(xiàn)，當(dāng)一種參與大腦發(fā)育的蛋白質(zhì)SRGAP3處于畸形狀態(tài)的話,，其就會(huì)引發(fā)小鼠大腦功能障礙，隨后就會(huì)引發(fā)和兒童神經(jīng)性障礙相似的一些癥狀表現(xiàn),。由于這種蛋白質(zhì)在人類機(jī)體中有類似的功能,，其或許是許多疾病障礙中缺失的一個(gè)環(huán)節(jié)，另外,，該蛋白質(zhì)的發(fā)現(xiàn)也可幫助研究者開發(fā)新型的以該蛋白質(zhì)為靶點(diǎn)的療法,。
研究者Dusan說，諸如精神分裂癥,、腦積水,、精神發(fā)育遲滯和自閉癥等大腦障礙對(duì)于兒童和年輕人來說是一種破壞性的疾病。我們希望我們的研究發(fā)現(xiàn)可以幫助研究者更好地理解疾病的發(fā)病過程以及開發(fā)出有效的療法,。
文章中,，研究者用SRGAP3蛋白失活的小鼠進(jìn)行實(shí)驗(yàn)，隨后研究者比較這種小鼠與正常小鼠的差異,，結(jié)果顯示,，SRGAP3蛋白失活的小鼠，其大腦解剖面發(fā)生了明顯的改變,，將會(huì)導(dǎo)致其行為類似于精神病人的行為,。不同腦功能障礙中涉及的SRGAP3蛋白質(zhì)表明這些障礙都是相關(guān)聯(lián)的，而且SRGAP3蛋白是大腦發(fā)育的一個(gè)關(guān)鍵蛋白質(zhì),。這些腦功能障礙或許是通過SRGAP3蛋白進(jìn)行相互連接的,，因?yàn)槠涠际峭ㄟ^干擾大腦神經(jīng)系統(tǒng)的發(fā)育來產(chǎn)生疾病的,。
最終,，研究者通過研究結(jié)果來從基因、蛋白質(zhì)乃至細(xì)胞信號(hào)通力和行為方面來理解大多數(shù)精神性疾病的復(fù)雜生物過程,，這可以幫助研究者開發(fā)出新型的靶向療法,。（生物谷Bioon.com）
編譯自：Single Protein Targeted as Root Biological Cause of Several Childhood Psychiatric Disorders
doi:10.1096/fj.11-202317
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Srgap3−/− mice present a neurodevelopmental disorder with schizophrenia-related intermediate phenotypes
Robert Waltereit*,†, Uwe Leimer*, Oliver von Bohlen und Halbach‖, Jutta Panke*, Sabine M. Hölter¶, Lillian Garrett¶, Karola Wittig§, Miriam Schneider‡, Camie Schmitt*, Julia Calzada-Wack#, Frauke Neff#, Lore Becker**,††, Cornelia Prehn**, Sergej Kutscherjawy*, Volker Endris‡‡, Claire Bacon‡‡, Helmut Fuchs**, Valérie Gailus-Durner**, Stefan Berger*, Kai Schönig*, Jerzy Adamski**, Thomas Klopstock††, Irene Esposito#§§, Wolfgang Wurst‖‖¶¶##, Martin Hrabě de Angelis**,***, Gudrun Rappold‡‡, Thomas Wieland§ and Dusan Bartsch*,1
Mutations in the SRGAP3 gene residing on chromosome 3p25 have previously been associated with intellectual disability. Genome-wide association studies have also revealed SRGAP3, together with genes from the same cellular network, as risk genes for schizophrenia. SRGAP3 regulates cytoskeletal dynamics through the RHO protein RAC1. RHO proteins are known to be involved in cytoskeletal reorganization during brain development to control processes such as synaptic plasticity. To elucidate the importance of SRGAP3 in brain development, we generated Srgap3-knockout mice. Ten percent of these mice developed a hydrocephalus and died before adulthood. Surviving mice showed various neuroanatomical changes, including enlarged lateral ventricles, white matter tracts, and dendritic spines together with molecular changes, including an increased basal activity of RAC1. Srgap3−/− mice additionally exhibited a complex behavioral phenotype. Behavioral studies revealed an impaired spontaneous alternation and social behavior, while long-term memory was unchanged. The animals also had tics. Lower locomotor activity was observed in male Srgap3−/− only. Srgap3−/− mice showed increased methylphenidate stimulation in males and an impaired prepulse inhibition in females. Together, the results show neurodevelopmental aberration in Srgap3−/− mice, with many of the observed phenotypes matching several schizophrenia-related intermediate phenotypes. Mutations of SRGAP3 may thus contribute to various neurodevelopmental disorders.—Waltereit, R., Leimer, U., von Bohlen und Halbach, O., Panke, J., Hölter, S. M., Garrett, L., Wittig, K., Schneider, M., Schmitt, C., Calzada-Wack, J., Neff, F., Becker, L., Prehn, C., Kutscherjawy, S., Endris, V., Bacon, C., Fuchs, H., Gailus-Durner, V., Berger, S., Schönig, K., Adamski, J., Klopstock, T., Esposito, I., Wurst, W., Hrabě de Angelis, M., Rappold, G., Wieland, T., Bartsch, D. Srgap3−/− mice present a neurodevelopmental disorder with schizophrenia-related intermediate phenotypes.
