The hyperactivity of the gene, which plays an important role in the development of the cerebral cortex, predisposes to schizophrenia, the research published in the journal Biological Psychiatry has shown.
Schizophrenia is a disease of the brain characterized by the so-called psychotic symptoms such as delusions, auditory and visual hallucinations. The disease most often appears in young people between 18 and 35 years of age.
Scientists have not yet known the exact cause of the development of schizophrenia. Research suggests that it is the resultant of certain inborn predispositions and the influence of environmental factors. The fact that genetic factors play an important role in its development is evidenced by the fact that the risk of developing schizophrenia increases from 1%. in the general population up to 10 percent. in people whose first degree relative (parent or sibling) has the condition. So far, scientists have identified several genes whose mutations are associated with an increased risk of the disease.
One of them is the NOS1AP gene, which encodes a protein that regulates the activity of neuronal nitric oxide synthase. In studies previously carried out in families where many relatives had schizophrenia, it was found that changes in the activity of this gene increase the risk of the disease.
To see how this happens, researchers at Rutger University in New Brunswick (NJ, USA) studied neuronal progenitor cells (i.e. the cells from which nerve cells develop) in the neocortex of rats. The neocortex is responsible for higher cognitive functions, such as memory, thinking, speech, as well as for the control of voluntary movements and the perception of external stimuli.
It turned out that the overactivity of the NOS1AP gene – and hence the overproduction of the protein it contains – disrupts the migration of neurons to the outermost layer of the neocortex, as well as the development of dendrites, i.e. extensions through which neurons communicate with each other. When gene activity was turned off, the migration of neurons to the outer layers of the neocortex increased.
According to the researchers, these results indicate that the NOS1AP gene plays an important role in the development of the cerebral cortex, and its hyperactivity may contribute to disturbances in its structure and neuronal connections, predisposing to schizophrenia.
“During brain development, a system of proper communication between neurons is established so that they can pass on information to each other. We have observed that in the case of NOS1AP hyperactivity, nerve cells do not move to the right places in the brain and do not have dendrites that branch to create the necessary connections, explains the lead author of the work, Prof. Bonnie Firestein.
The researcher reminds that in patients with schizophrenia there are disturbances in the connections between neurons and structural changes in the prefrontal cortex. This area of the brain matures eventually in early adulthood, when the disease is most often diagnosed.
In the future, prof. Firestein plans to check whether antipsychotics used in the treatment of patients with schizophrenia are able to counteract the overproduction of the protein written in the NOS1AP gene. (PAP)