Too much protein expressed by a gene associated with schizophrenia causes faulty connections between nerve cells and keeps them from branching out and communicating with each other, according to a new study with rats.
The findings about the NOS1AP gene may help explain the biological process of the disease, researchers say.
The study, published online in the journal Biological Psychiatry, shows that an overabundance of the protein causes dendrites—the tree-like structures that allow cells to talk to each other and are essential to the functioning of the nervous system—to become stunted in the developing brains of rats.
This keeps the dendrites 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 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 Bonnie Firestein, professor of cell biology and neuroscience at Rutgers.
“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.
While about 1 percent of the general population suffers from schizophrenia, the risk increases to about 10 percent in the first degree relatives of an individual with the disease. NOS1AP has been identified as a risk factor in some families with multiple individuals affected with schizophrenia.
Since the prefrontal cortex, the part of the brain that is associated with schizophrenia matures through adulthood, Firestein says it is possible that drug treatment therapies could be developed to target the disease in adolescents, when schizophrenia is thought to develop and when symptoms appear.
“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,” says Firestein.
Linda Brzustowicz, professor and chair of the genetics department at Rutgers, is a coauthor of the paper.