title: Mitochondrial dysfunction bridges negative affective disorders and cardiomyopathy in socially isolated rats: Pros and cons of fluoxetine.
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, 7.5 mg/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 (7.5 mg/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.
authors.affiliation: a Zanjan Applied Pharmacology Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.|b Department of Pharmacology and Toxicology, School of Pharmacy , Zanjan University of Medical Sciences , Zanjan , Iran.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Sonei
authors.affiliation: c Department of Pharmacology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.|d Experimental Medicine Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Shayan
authors.initials: S
authors.lastname: Amiri
authors.affiliation: a Zanjan Applied Pharmacology Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.|b Department of Pharmacology and Toxicology, School of Pharmacy , Zanjan University of Medical Sciences , Zanjan , Iran.
authors.forename: Iman
authors.initials: I
authors.lastname: Jafarian
authors.affiliation: a Zanjan Applied Pharmacology Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.|b Department of Pharmacology and Toxicology, School of Pharmacy , Zanjan University of Medical Sciences , Zanjan , Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Anoush
authors.affiliation: e Department of Human Anatomy and Cell Science , College of Medicine, Faculty of Health Sciences, University of Manitoba , Winnipeg , Manitoba , Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahimi-Balaei
authors.affiliation: e Department of Human Anatomy and Cell Science , College of Medicine, Faculty of Health Sciences, University of Manitoba , Winnipeg , Manitoba , Canada.
authors.forename: Hugo
authors.initials: H
authors.lastname: Bergen
authors.affiliation: c Department of Pharmacology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.|d Experimental Medicine Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Arya
authors.initials: A
authors.lastname: Haj-Mirzaian
authors.affiliation: a Zanjan Applied Pharmacology Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.|b Department of Pharmacology and Toxicology, School of Pharmacy , Zanjan University of Medical Sciences , Zanjan , Iran.
authors.forename: Mir-Jamal
authors.initials: MJ
authors.lastname: Hosseini
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight; D001921:Brain / Q000187:drug effects; D009202:Cardiomyopathies / Q000503:physiopathology* / Q000523:psychology; D003863:Depression / Q000188:drug therapy; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000008:administration & dosage; D006321:Heart / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000473:pathology*; D019964:Mood Disorders / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Depression; brain; heart; mitochondrial dysfunction; social isolation stress