About The Gazette Search Back Issues Contact Us    
The newspaper of The Johns Hopkins University October 22, 2007 | Vol. 37 No. 8
Normal Role for Major Schizophrenia Risk Gene Identified

Disc1 makes protein that helps new neurons integrate into neural net

By Nick Zagorski
Johns Hopkins Medicine

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 Johns Hopkins researchers and their colleagues, appearing online in Cell Sept. 6, 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," said Hongjun Song, an associate professor at Johns 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."

Added fellow author Guo li Ming, also an associate professor at ICE, "Almost every part of the nerve integration process speeds up. 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 the University of California, 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 Johns 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.

The research was funded by the National Institutes of Health, McKnight Scholar Award, Whitehall Foundation and a Klingenstein Fellowship Award in the Neurosciences.

Authors on the paper are Jay Chang, Sundar Ganesan and Bai Lu, all of the National Institutes of Mental Health; Regina Faulkner, Xiao bo Liu and Hwai Jong Cheng, all 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, Ming and Song, all of Johns Hopkins.


Related Web sites

Hongjun Song


The Gazette | The Johns Hopkins University | Suite 540 | 901 S. Bond St. | Baltimore, MD 21231 | 443-287-9900 |