The Impacts of Vorinostat on Nadph Oxidase and Mitochondrial Biogenesis Gene Expression in the Heart of Mice Model of Depression Publisher Pubmed



Nasehi L^{1, 2} ; Morassaei B³ ; Ghaffari M³ ; Sharafi A^{4, 5} ; Dehpour AR^{6, 7} ; Hosseini MJ³ Show Affiliations
Source: Canadian Journal of Physiology and Pharmacology Published:2022

Abstract

The comorbidity of depression and high risk of cardiovascular diseases (CVD) have been reported as major health problems. Our previous study confirmed that fluoxetine (FLX) therapy had a significant influence on brain function but not on the heart in depression. In the present study, suberoyanilide hydroxamic acid (SAHA) was proposed as another therapeutic candidate for treatment of depression comorbid CVD in maternal separation model, following behavioral analyses and gene expression level in the heart. Our data demonstrated that SAHA significantly attenuates the NOX-4 gene expression level in treated mice with SAHA and FLX without significant change in NOX-2 expression level. SAHA decreased the gene expression level of peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) and nuclear respiratory factors (Nrf2) in heart tissues of maternally separated mice. It supposed that non-effectiveness of FLX on mitochondrial biogenesis and NOX gene expression level in the heart of depressed patient can be related to recurrence of depression. It revealed that SAHA not only reversed the depressive-like behavior similar to our previous data but also recovered the heart mitochondrial function via effect on NOX-2, NOX-4, and mitochondrial biogenesis genes’ (PGC-1α, Nrf-2, and peroxisome proliferator-activated receptor-α (PPAR-α)) expression levels. We suggest performing more studies to confirm SAHA as a therapeutic candidate in depression comorbid CVD. © 2022 The Author(s).