Researchers at Rutgers report that a gene associated with schizophrenia plays a role in brain development and may help to explain the biological process of the disease. The team published its study (“NOS1AP, a protein implicated in schizophrenia, controls radial migration of cortical neurons”) in Biological Psychiatry.
Bonnie Firestein, Ph.D., professor in the department of cell biology and neuroscience, says too much protein expressed by the NOS1AP gene, which has been associated with schizophrenia, causes abnormalities in brain structure and faulty connections between nerve cells that prevent them from communicating properly.
Dr. Firestein’s research indicates that an overabundance of a protein in the NOS1AP gene resulted in the dendrites being stunted in the developing brains of rats. She and her colleagues found that too much of the NOS1AP protein in brain cells didn't allow them to branch out and kept them deep within the neocortex, the portion of the brain responsible for higher functioning skills, such as spatial reasoning, conscious thought, motor commands, language development, and sensory perception.
In the control group of rats in which NOS1AP chemical protein was not overexpressed, the cellular connections developed properly, with cells moving out to the outer layers of the neocortex and enabling the nerve cells to communicate.
“When the brain develops, it sets up a system of the right type of connectivity to make sure that communication can occur,” says Dr. Firestein. “What we saw here was that the nerve cells didn't move to the correct locations and didn't have dendrites that branch out to make the connections that were needed.”
Although scientists can't pinpoint for certain the exact cause of schizophrenia, they have determined that several genes, including NOS1AP, are associated with an increased risk for the disabling brain disorder and believe that when there is an imbalance of the chemical reactions in the brain, development can be disrupted.
“NOS1AP overexpression disrupts neuronal migration, resulting in increased cells in IZ [intermediate zone] and less cells in CP [cortical plate], and decreases dendritogenesis,” wrote the investigators. “Knock down results in increased migration, with more cells reaching the CP. The phosphotyrosine binding region, but not the PDZ-binding motif, is necessary for NOS1AP function. Amino acids 181-307, which are sufficient for NOS1AP-mediated decreases in dendrite number, have no effect on migration.
“Our studies show for the first time a critical role for the schizophrenia-associated gene NOS1AP in cortical patterning, which may contribute to underlying pathophysiology seen in schizophrenia.”
“The next step would be to let the disease develop in the laboratory and try to treat the over expression of the protein with an antipsychotic therapy to see if it works,” explains Dr. Firestein.
