Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

Mitochondrial dysfunction bridges negative affective disorders and cardiomyopathy in socially isolated rats: Pros and cons of fluoxetine

(2017) Mitochondrial dysfunction bridges negative affective disorders and cardiomyopathy in socially isolated rats: Pros and cons of fluoxetine. World Journal of Biological Psychiatry. pp. 39-53. ISSN 1562-2975

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Abstract

Objectives Depression is tightly associated with cardiovascular comorbidity and accounts for high financial and social burden worldwide. Mitochondrial dysfunction contributes to the pathophysiology of depression and cardiovascular disorders; its contribution to depression-cardiovascular comorbidity has not yet been investigated. Methods Adolescent rats were subjected to 4 weeks of isolation (social isolation stress or SIS) or social conditions (control), and then they were divided into treatment (fluoxetine, 7.5mg/kg/day for 21 days) and non-treatment groups. After different housing conditions and treatment, animals were evaluated by behavioural tests (n=6-8) and mitochondrial assessments (n=3) of brain and cardiac tissues. Results We found that juvenile SIS induced behavioural abnormalities and mitochondrial dysfunction in adulthood. We showed that juvenile SIS was associated with impaired respiratory chain complex, which leads to reactive oxygen species formation, oxidative damage and ATP abatement in both brain and heart. Administration of FLX (7.5mg/kg/day) during the isolation period attenuated the effects of SIS on the brain mitochondria and behavioural abnormalities, but had little or no effect on SIS-induced mitochondrial dysfunction in cardiac tissue. Conclusions This suggests that juvenile SIS predisposes the co-occurrence of depression and cardiovascular disease through mitochondrial dysfunction and that therapeutic effect of fluoxetine is partly mediated by its effect on mitochondrial function.

Item Type: Article
Keywords: Depression brain heart mitochondrial dysfunction social isolation stress GLUCOCORTICOID-RECEPTOR PHOSPHORYLATION MAJOR DEPRESSIVE DISORDER ELEVATED PLUS-MAZE ENERGY-METABOLISM CARDIAC MYOCYTES STRESSED RATS NEUROPSYCHIATRIC DISORDERS LIVER-MITOCHONDRIA OXIDATIVE STRESS NMDA RECEPTORS Psychiatry
Page Range: pp. 39-53
Journal or Publication Title: World Journal of Biological Psychiatry
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q2
Volume: 18
Number: 1
Identification Number: https://doi.org/10.3109/15622975.2016.1149218 <Go to ISI>://WOS:000393977000004
ISSN: 1562-2975
Depositing User: خانم مریم زرقانی
URI: http://repository.zums.ac.ir/id/eprint/190

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