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Clozapine Attenuates Mitochondrial Dysfunction, Inflammatory Gene Expression, and Behavioral Abnormalities in an Animal Model of Schizophrenia Publisher Pubmed



Amiri S1 ; Dizaji R2 ; Momeny M3 ; Gauvin E4 ; Hosseini MJ2, 5
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology, College of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
  3. 3. Hematology/Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada
  5. 5. Departments of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran

Source: Neuropharmacology Published:2021


Abstract

Beyond abnormalities in the neurotransmitter hypothesis, recent evidence suggests that mitochondrial dysfunction and immune-inflammatory responses contribute to the pathophysiology of schizophrenia. The prefrontal cortex (PFC) undergoes maturation and development during adolescence, which is a critical time window in life that is vulnerable to environmental adversities and the development of psychiatric disorders such as schizophrenia. Applying eight weeks of post-weaning social isolation stress (PWSI) to rats, as an animal model of schizophrenia, we decided to investigate the effects of PWSI on the mitochondrial function and expression of immune-inflammatory genes in the PFC of normal and stressed rats. To do this, control and PWSI rats were divided into treatment (clozapine; CLZ, 2.5 mg/kg/day for 28 days) and non-treatment sub-groups. Our results showed PWSI caused schizophrenic-like behaviors in rats and induced mitochondrial dysfunction as well as upregulation of genes associated with innate immunity in the PFC. Chronic treatment with CLZ attenuated the effects of PWSI on behavioral abnormalities, mitochondrial dysfunction, and immune-inflammatory responses in the PFC of rats. These results may advance our understanding about the mechanism of action of CLZ that targets mitochondrial dysfunction and immune-inflammatory responses as factors involved in the pathophysiology of schizophrenia. © 2021 Elsevier Ltd
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