An excess of long isoform nitric oxide synthase 1 adaptor protein, or NOS1AP, may be a cause of schizophrenia development, according to findings from Rutgers University.
Schizophrenia may be explained by a related gene’s role in brain development, according to findings published in the journal, Biological Psychiatry.
Researchers from Rutgers University, New Brunswick, NJ, examined the long isoform nitric oxide synthase 1 adaptor protein (NOS1AP), a protein encoded by a susceptibility gene for schizophrenia, in order to determine the pathways by which the gene becomes aberrant and the disease is introduced. The researchers studied animal models of the normal and over-expressed levels of NOS1AP.
The cellular connections in the normal NOS1AP level brains developed in the usual fashion: cells moved to the outer layers of the neocortex which enabled the nerve cells to communicate. When there was an over expression of NOS1AP, proteins in the brain cells — the dendrites, which allow communication between the cells – were prohibited from branching out and they were housed deep inside the neocortex. The neocortex is the region responsible for higher functioning skills such as spatial reasoning, conscious thought, motor commands, language development, and sensory perception.
“When the brain develops, it sets up a system of the right type of connectivity to make sure that communication can occur,” Bonnie Firestein, PhD explained in a press release. “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.”
A secondary conclusion the researchers found was that proper NOS1AP function required the phosphotyrosine binding region, but not the PDZ binding motif. No effect on migration was found to be caused by amino acids 181 to 207, although they are sufficient for NOS1AP mediated decreases in the dendrite number.
Prior research has been so far unable to identify the specific cause of schizophrenia. However, they have been successful in confirming a few genes, including NOS1AP, are associated with increased risk of the disorder. Researchers generally believe that an imbalance of chemicals in the brain can cause development disruptions.
Firestein believed it was possible that drug treatment therapies could be developed to target schizophrenia in adolescents, which is when the disorder is thought to develop and when symptoms typically appear. The prefrontal cortex, where schizophrenia is believed to be housed, matures through adolescence and adulthood, which may allow drug therapies to be successful.
“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 anti-psychotic therapy to see if it works,” Firestein concluded.