Although scientists still do not know what causes schizophrenia or how to cure it, they are investigating the brain processes behind this severe disease. Now, an experiment in rodents has uncovered a key role in the chemical imbalance of a compound called kinurenic acid (KYNA) and its effects on schizophrenia-like symptoms.
Previous research had suggested that kinuranic acid plays a key role in the pathophysiology of schizophrenia , as people with schizophrenia have higher levels of kinurenic acid than healthy individuals. In addition, the presence of KYNA is also associated with a decrease in the levels of the amino acid glutamate.
Could this reduction in glutamate levels in the brain explain the brain dysfunction of schizophrenia?
Based on this approach, a team of scientists from the University of Maryland School of Medicine in Baltimore (USA) set out to investigate the pathological role of KYNA in mice and the connection with schizophrenia-like behavior.
Mouse experiment
To carry out the study, the scientists used mice genetically modified to show a deficiency of kinurenine 3-monooxygenase (KMO), an enzyme that plays a key role in the metabolism of KYNA in the brain. Thus, the lower the KMO presence, the higher the KYNA level and vice versa. In six trials, they performed genomic analyzes of differential gene expression in the rodent cerebral cortex and cerebellum and various tests.
The results determined that mice with lower levels of KMO showed alterations in contextual memory and spent less time interacting with their congeners. In addition, they showed greater anxiety when facing a challenge, such as escaping from a maze. They also found higher levels of KYNA in the cerebellum than in the brain.
Since increased anxiety, lack of desire to socialize, and impaired contextual memory are typical symptoms of schizophrenia, the study suggests that KMO and KYNA are crucial factors in the disease.
“This study provides crucial new support for our long-standing hypothesis, and explains how the KYNA system can become dysfunctional in schizophrenia,” explains Robert Schwarcz, leader of the work.
The study has been published in the journal Biological Psychiatry.
