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 effect...

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Main Authors: Yosra Magdy, Sherif Kamar, Hoda Fansa, Sara Khedr, Amina Sedky
Format: Article
Language:English
Published: SpringerOpen 2025-04-01
Series:The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
Subjects:
Online Access:https://doi.org/10.1186/s41983-025-00960-x
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author Yosra Magdy
Sherif Kamar
Hoda Fansa
Sara Khedr
Amina Sedky
author_facet Yosra Magdy
Sherif Kamar
Hoda Fansa
Sara Khedr
Amina Sedky
author_sort Yosra Magdy
collection DOAJ
description 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.
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spelling doaj-art-0fc41516ea174f7abf3a4fbfa3da394e2025-08-20T03:52:23ZengSpringerOpenThe Egyptian Journal of Neurology, Psychiatry and Neurosurgery1687-83292025-04-0161111310.1186/s41983-025-00960-xComparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in miceYosra Magdy0Sherif Kamar1Hoda Fansa2Sara Khedr3Amina Sedky4Ain Shams UniversityAl-Ahliyya Amman UniversityAl-Ahliyya Amman UniversityAin Shams UniversityAin Shams UniversityAbstract 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.https://doi.org/10.1186/s41983-025-00960-xTrimetazidineOlanzapineKetamineSchizophreniaMitochondriaCognitive function
spellingShingle Yosra Magdy
Sherif Kamar
Hoda Fansa
Sara Khedr
Amina Sedky
Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice
The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
Trimetazidine
Olanzapine
Ketamine
Schizophrenia
Mitochondria
Cognitive function
title Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice
title_full Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice
title_fullStr Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice
title_full_unstemmed Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice
title_short Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice
title_sort comparative study trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine induced psychosis model in mice
topic Trimetazidine
Olanzapine
Ketamine
Schizophrenia
Mitochondria
Cognitive function
url https://doi.org/10.1186/s41983-025-00960-x
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