Cell：精神分裂致病基因在大脑中的正常功能
生物谷报道：导致影响着数百万美国人的精神分裂和其它精神科疾病的基因的致病机制还不清楚，但由Johns Hopkins科学家进行的新研究发现了这一基因在正常大脑中作用，结果发表在本周的Cell上。
文章表示，这一被称为disc1的基因会产生一种蛋白，该蛋白充当了成年大脑中新产生神经元的指挥，disc1指挥它们以合适的节奏到达正确的位置，这样神经元就可以很好的结合到我们复杂的神经系统中。一旦disc1蛋白不正常，新神经元也无法到达正确位置。
Hopkins细胞工程研究所副教授Hongjun Song说：“DISC1在成年神经发育过程中起的作用比想象的还要大。之前的研究认为DISC1对神经移动和扩展很重要。而我们针对老鼠的研究显示DISC1作用不止如此，这或许能解释DISC1为何会造成多种精神疾病。”
文章另一作者，ICE副教授Guo-li Ming说：“几乎神经系统每个部分都加速了，包括神经迁移和扩展、形成新连接，它们甚至对电刺激更敏感。”Song注意到由于大脑的复杂性，因此合适的时间对于保证新神经元插入神经网络的准备很重要。
Ming，Song和同事通过向老鼠大脑的海马体注入特殊病毒来追踪过度活跃的脑神经元的异常活动。海马主管学习记忆，因此和精神疾病相关。病毒只感染新神经元，抑制其中disc1基因表达，并使神经在显微镜下发光。
利用Hopkins最近发明的DISC1异常的老鼠模型，科学家能复制出焦虑、兴奋、冷漠等症状，而了解蛋白的正常功能对于揭开复杂精神疾病的病因很重要。Song和Ming正计划进一步针对老鼠进行实验。（教育部科技发展中心）
原始出处:
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
gming1@jhmi.edu
Corresponding author
Bai Lu
bailu@mail.nih.gov
Corresponding author
Hongjun Song
shongju1@jhmi.edu
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.
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