Comparative study: Trimetazidine vs Olanzapine on cognitive dysfunction and behavioral changes in Ketamine-induced psychosis model in mice
Yosra M. Magdy, Sherif A. Kamar, Hoda A. Fansa, Sara Khedr, Amina Sedky
preprint DOI: 10.21203/rs.3.rs-5020062/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study |
|---|---|
| Population | Mice with ketamine-induced psychosis |
| Interventions | Trimetazidine Olanzapine Ketamine |
| Topics | Esketamine Ketamine |
| Key findings | In mice with ketamine-induced psychosis, trimetazidine improved cognitive function and raised BDNF, lowered MDA, and increased skeletal muscle PGC1-alpha and plasma irisin, effects the authors describe as exercise-like. Olanzapine produced less cognitive improvement and reduced PGC1-alpha and muscle grip. The authors propose trimetazidine as an alternative to exercise for schizophrenia patients with cognitive dysfunction. |
Abstract
Abstract Mitochondrial dysfunction and oxidative stress may contribute to schizophrenia. Negative symptoms and cognitive dysfunction in individuals with schizophrenia are resistant to antipsychotic medications, but physical exercise is an effective treatment. Beneficial effects of exercise involve the release of 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 increase irisin re-lease, 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. 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. 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.