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的作用，结果发表在近期的《细胞》（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。
原文链接：
Normal role for schizophrenia risk gene identified
How the gene that has been pegged as a major risk factor for schizophrenia and other mood disorders that affect millions of Americans contributes to these diseases remains unclear. However, the results of a new study by Hopkins researchers and their colleagues, appearing in Cell this week, provide a big clue by showing what this gene does in normal adult brains.
It turns out that this gene, called disc1, makes a protein that serves as a sort of musical conductor for newly made nerve cells in the adult brain, guiding them to their proper locations at the appropriate tempo so they can seamlessly integrate into our complex and intertwined nervous system. If the DISC1 protein doesn’t operate properly, the new nerves go hyper.
“DISC1 plays a broader role in the development of adult nerves than we anticipated,” says Hongjun Song, Ph.D., an associate professor at Hopkins’ Institute for Cell Engineering. “Some previous studies hinted that DISC1 is important for nerve migration and extension, but our study in mice suggests it is critical for more than that and may highlight why DISC1 is associated with multiple psychiatric disorders.”
“Almost every part of the nerve integration process speeds up,” adds fellow author Guo-li Ming, M.D., Ph.D., also an associate professor at ICE. “The new nerves migrate and branch out faster than normal, form connections with neighbors more rapidly, and are even more sensitive to electrical stimulation.”
While it may not be obvious why high-speed integration would be detrimental, Song notes that because of the complexity of the brain, timing is critical to ensure that new nerves are prepared to plug into the neural network.
“DISC1 plays a broader role in the development of adult nerves than we anticipated,” says Hongjun Song, Ph.D., an associate professor at Hopkins’ Institute for Cell Engineering. “Some previous studies hinted that DISC1 is important for nerve migration and extension, but our study in mice suggests it is critical for more than that and may highlight why DISC1 is associated with multiple psychiatric disorders.”
“Almost every part of the nerve integration process speeds up,” adds fellow author Guo-li Ming, M.D., Ph.D., also an associate professor at ICE. “The new nerves migrate and branch out faster than normal, form connections with neighbors more rapidly, and are even more sensitive to electrical stimulation.”
While it may not be obvious why high-speed integration would be detrimental, Song notes that because of the complexity of the brain, timing is critical to ensure that new nerves are prepared to plug into the neural network.
Ming, Song and their collaborators at the National Institutes of Health and UC Davis tracked the abnormal movements of the hyperactive nerve cells by injecting a specially designed virus into a part of a mouse brain known as the hippocampus -a region important for learning and memory and therefore quite relevant to psychiatric disorders. The virus would only infect newly born cells and would both knock down the expression of the disc1 gene and make the nerves glow under a microscope.
Combined with other recent Hopkins research that successfully engineered mouse models that have abnormal DISC1 and can effectively reproduce schizophrenia symptoms such as anxiety, hyperactivity, apathy and altered senses, these current findings teasing out the normal role of this protein may help unravel the causes for this complex disease
Song and Ming add that their studies in the hippocampus - one of the few places where new nerves are made in the adult brain - might answer why symptoms typically first appear in adults despite the genetic basis of many psychiatric illnesses. They plan on continuing their mouse work to try and find those answers.
Source: Johns Hopkins Medical Institutions
Combined with other recent Hopkins research that successfully engineered mouse models that have abnormal DISC1 and can effectively reproduce schizophrenia symptoms such as anxiety, hyperactivity, apathy and altered senses, these current findings teasing out the normal role of this protein may help unravel the causes for this complex disease
Song and Ming add that their studies in the hippocampus - one of the few places where new nerves are made in the adult brain - might answer why symptoms typically first appear in adults despite the genetic basis of many psychiatric illnesses. They plan on continuing their mouse work to try and find those answers.
Source: Johns Hopkins Medical Institutions
