生物谷報道：導致影響著數(shù)百萬美國人的精神分裂和其它精神科疾病的基因的致病機制還不清楚,，但由Johns Hopkins科學家進行的新研究發(fā)現(xiàn)了這一基因在正常大腦中作用,，結果發(fā)表在本周的Cell上,。
文章表示,，這一被稱為disc1的基因會產(chǎn)生一種蛋白,，該蛋白充當了成年大腦中新產(chǎn)生神經(jīng)元的指揮，disc1指揮它們以合適的節(jié)奏到達正確的位置,，這樣神經(jīng)元就可以很好的結合到我們復雜的神經(jīng)系統(tǒng)中,。一旦disc1蛋白不正常，新神經(jīng)元也無法到達正確位置,。
Hopkins細胞工程研究所副教授Hongjun Song說：“DISC1在成年神經(jīng)發(fā)育過程中起的作用比想象的還要大,。之前的研究認為DISC1對神經(jīng)移動和擴展很重要。而我們針對老鼠的研究顯示DISC1作用不止如此,，這或許能解釋DISC1為何會造成多種精神疾病,。”
文章另一作者，ICE副教授Guo-li Ming說：“幾乎神經(jīng)系統(tǒng)每個部分都加速了,，包括神經(jīng)遷移和擴展,、形成新連接，它們甚至對電刺激更敏感,。”Song注意到由于大腦的復雜性,，因此合適的時間對于保證新神經(jīng)元插入神經(jīng)網(wǎng)絡的準備很重要。
Ming,，Song和同事通過向老鼠大腦的海馬體注入特殊病毒來追蹤過度活躍的腦神經(jīng)元的異?；顒印：ｑR主管學習記憶,，因此和精神疾病相關,。病毒只感染新神經(jīng)元，抑制其中disc1基因表達,，并使神經(jīng)在顯微鏡下發(fā)光,。
利用Hopkins最近發(fā)明的DISC1異常的老鼠模型,，科學家能復制出焦慮、興奮,、冷漠等癥狀,，而了解蛋白的正常功能對于揭開復雜精神疾病的病因很重要。Song和Ming正計劃進一步針對老鼠進行實驗,。（教育部科技發(fā)展中心）
原始出處:
Cell, Vol , Issue , Article
Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain
Xin Duan,1,2 Jay H. Chang,3 Shaoyu Ge,1,4 Regina L. Faulkner,5 Ju Young Kim,1,4 Yasuji Kitabatake,1,4 Xiao-bo Liu,5 Chih-Hao Yang,1,4 J. Dedrick Jordan,1,4 Dengke K. Ma,1,2 Cindy Y. Liu,1 Sundar Ganesan,6 Hwai-Jong Cheng,5 Guo-li Ming,1,2,4, Bai Lu,3,6, and Hongjun Song1,2,4,
1 Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
2 The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
3 Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
4 Department of Neurology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
5 Center for Neuroscience, University of California, Davis, 1544 Newton Court, Davis, CA 95616, USA
6 Section on Neural Development, National Institute of Child Health and Human Developmental Health, National Institutes of Health, Bethesda, MD 20892, USA
Corresponding author
Guo-li Ming
[email protected]
Corresponding author
Bai Lu
[email protected]
Corresponding author
Hongjun Song
[email protected]
Summary
Adult neurogenesis occurs throughout life in discrete regions of the adult mammalian brain. Little is known about the mechanism governing the sequential developmental process that leads to integration of new neurons from adult neural stem cells into the existing circuitry. Here, we investigated roles of Disrupted-In-Schizophrenia 1 (DISC1), a schizophrenia susceptibility gene, in adult hippocampal neurogenesis. Unexpectedly, downregulation of DISC1 leads to accelerated neuronal integration, resulting in aberrant morphological development and mispositioning of new dentate granule cells in a cell-autonomous fashion. Functionally, newborn neurons with DISC1 knockdown exhibit enhanced excitability and accelerated dendritic development and synapse formation. Furthermore, DISC1 cooperates with its binding partner NDEL1 in regulating adult neurogenesis. Taken together, our study identifies DISC1 as a key regulator that orchestrates the tempo of functional neuronal integration in the adult brain and demonstrates essential roles of a susceptibility gene for major mental illness in neuronal development, including adult neurogenesis.
