Schizophrenia Risk Gene DISC1 Plays a Broader Role in the Development of Nervous System
Sep 10, 2007 - 4:19:08 AM
, Reviewed by: Dr. Himanshu Tyagi
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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
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Level of Evidence
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2c - Outcomes Research
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Key Points of this article
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DISC1 plays a broader role in the development of adult nerves than we anticipated
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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.
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Main results
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Gene 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.
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DISC1 Gene
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Millar et al. (2000) isolated and sequenced a translocation breakpoint region on chromosome 1q42 that had been identified by St. Clair et al. (1990) in a large Scottish family with mental and/or behavioral disorders, including schizophrenia (see 181500), schizoaffective disorder, recurrent major depression, and adolescent conduct and emotional disorders (see also 603342). Within the 1q42 chromosomal region, Millar et al. (2000) identified 2 novel genes directly disrupted by the translocation, which the authors termed 'disrupted in schizophrenia' 1 and 2 (DISC1 and DISC2, 606271).
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By Johns Hopkins Medicine,
[RxPG] 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.
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.
Original research article:
http://download.cell.com/pdfs/0092-8674/PIIS0092867407008975.pdf
Publication:
Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain; Xin Duan, Jay H. Chang, Shaoyu Ge, Regina L. Faulkner, Ju Young Kim, Yasuji Kitabatake, Xiao-bo Liu, Chih-Hao Yang, J. Dedrick Jordan, Dengke K. Ma, Cindy Y. Liu, Sundar Ganesan, Hwai-Jong Cheng, Guo-li Ming, Bai Lu, and Hongjun Song; 10.1016/j.cell.2007.07.010
On the web:
http://www.hopkins-ice.org/neuro/int/song.html
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Funding information and declaration of competing interests:
The research was funded by the National Institutes of Health, McKnight Scholar Award, Whitehall Foundation and a Klingenstein Fellowship Award in the Neurosciences
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About Dr. Himanshu Tyagi
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This news story has been reviewed by Dr. Himanshu Tyagi before its publication on RxPG News website. Dr. Himanshu Tyagi, MBBS is the founder editor and manager for RxPG News. In this position he is responsible for content development and overall website and editorial management functions. His areas of special interest are psychological therapies and evidence based journalism.
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
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Additional information about the news article
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Authors on the paper are Jay Chang, Sundar Ganesan & Bai Lu of the National Institutes of Mental Health; Regina Faulkner, Xiao-bo Liu & Hwai-Jong Cheng of the University of California, Davis; and Xin Duan, Shaoyu Ge, Ju Young Kim, Yasuji Kitabatake, Chih-Hao Yang, J. Dedrick Jordan, Dengke Ma, Cindy Liu, Guo-li Ming and Hongjun Song of Hopkins.
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