Approximately 3.5 million people in the US have been diagnosed with schizophrenia. Although various therapies are available to treat and manage the illness, so far, there is no cure (Smith, 2019). From experimenting on mice, however, researchers from Columbia University have not only found that a gene previously linked to schizophrenia, known as SETD1A, is a likely precursor for the illness, but also a way to possibly alleviate its effects.
In their study, the researchers genetically engineered mice to have a malfunctioning version of SETD1A, an enzyme-coding gene, and then tested them on key traits linked with schizophrenia. From their results, they found that the mice with the faulty genes tended to make mistakes on tasks where they navigated a maze to receive a reward. Furthermore, they found deficits in their working memory too- the ability to hold information and then retrieve it to guide their behavior- an impairment also found in schizophrenic patients.
Further studying their brains, the researchers then found that the faulty gene disrupted their neuronal networks, reducing the capacity of their neurons to communicate. For example, they found that it both stunted the growth and branching of cell extensions and reduced the number of spines on them; these needed to transfer chemical signals from neighbouring cells into electrical impulses (Anderton: 2019).
Beyond simply affecting a singular process, the researchers further found that the faulty SETD1A gene also disputed the regulation of many other genes with which it interacted. They found that whole classes of other genes were either under-expressed or over-expressed, depending on how they interacted with SETD1A.
To see how to remedy the effects of this faulty gene, the researchers experimentally introduced a healthy SETD1A gene into the mice, something that restored their working memory. Next inhibiting the expression of a gene called LSD1, known to counteract SETD1A, they managed to correct all of the mice’s behavioural and neuronal abnormalities. Although the brains of mice somewhat differ from those in humans, the researchers nevertheless suspect that many of these functionalities may have been preserved throughout evolution and so may also be present in humans.
According to Joseph Gogos, the leader of the study, “Although SETD1A mutations exist in a small percentage of all schizophrenia patients, many people diagnosed with the disorder have issues similar to those caused by this mutation. Thus, therapies that are specific to SETD1A may indeed have wider implications for schizophrenia as a whole (National Institute of Mental Health”: 2019).”
National Institute of Mental Health: Science Daily