Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice

Abstract

Background: Mitochondrial dysfunction and oxidative stress may contribute to schizophrenia. Negative symptoms and cognitive dysfunction in individuals with schizophrenia are resistant to anti-psychotic medications, but physical exercise is an effective treatment. Exercise’s beneficial effects involve releasing irisin from skeletal muscle by activating mitochondrial peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC1-α). “Irisin enhances cognitive function by boosting brain-derived neurotrophic factor (BDNF) and through its antioxidant properties.” Schizophrenia patients struggle to engage in physical activity due to dysfunction in their skeletal muscle mitochondria. Trimetazidine improves mitochondrial function and increases irisin release, offering an alternative to exercise for schizophrenics with cognitive dysfunction. The study compared trimetazidine to olanzapine in treating behavioral changes and cognitive dysfunction in mice with ketamine-induced psychosis. Researchers investigated the effects of trimetazidine on muscle power, mitochondrial function, plasma irisin level, and their correlation with hippocampal BDNF and MDA. Results: Ketamine use in mice led to cognitive dysfunction, reduced BDNF, elevated MDA, decreased muscle grip, and irisin. Trimetazidine improved irisin and improved BDNF, MDA levels, and cognitive function. Conclusions: Trimetazidine works like exercise, leading to an increase in skeletal muscle mitochondrial PGC1α and plasma irisin. Olanzapine induced less improvement in cognitive function with a reduction in PGC1α and muscle grip.