The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction

Yiming Wang,Dongfeng Zhang,Xingde Liu,Michael Berk,Jianhui Chen,Shuzheng Liu

doi:10.1186/1741-7015-11-32

Abstract

BackgroundThere is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear. Our previous study demonstrated an increase in pro-apoptotic pathways in the myocardium and hippocampus in MDD, which was reversed by venlafaxine. This study aimed to attempt to confirm the effects of apoptosis vulnerability markers on the myocardium in a model of depression after myocardial infarction.MethodsRats were divided into four groups: sham (N = 8), depression (N = 8, chronic mild unpredictable stress and separation were used in the depression group), MI (N = 13) and post-MI depression (N = 7). The rats in all four groups underwent the same open field and sucrose preference behavioral tests. Evan Blue staining was used to determine the area at risk of myocardial infarction in the left ventricle, and 2,3,5-triphenyl tetrazolium chloride (1.5% TTC) dye was used to detect the size of the myocardial infarction. The expression of bax and bcl-2 protein in the myocardium was investigated by immunohistochemistry, and the mRNA expression of bax, bcl-2 and caspase-3 in the myocardium was investigated by real time RT-PCR. Apoptosis was estimated in the myocardium by measuring the Bax:Bcl-2 ratio.ResultsIn the depression and post-MI depression rats, there were significantly decreased movements and total sucrose consumption, modeling behavioral deficits and an anhedonic-like state. In terms of myocardial infarction size, no difference was seen between the MI and post-MI depression groups. There was an up-regulated Bax:Bcl-2 ratio in the depression, MI and post-MI depression groups. Furthermore, in the latter group, there was a greater up-regulated Bax:Bcl-2 ratio. However, caspase-3 did not differ among the four groups.ConclusionsThese results of this animal model suggest that active pro-apoptotic pathways may be involved in the nexus between myocardial infarction and depression. This mechanism may be germane to understanding this relationship in humans.

Highlights

There is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear
Animals were managed in accordance with the American Psychological Association (APA) ethical standards in the treatment of rats and National Institute of Health and Guide for the Care and Use of Laboratory Animals (NIH Publications No 80-23) revised in 1996, and the study was approved by the ethics Committee on the Guidelines for Animal Experiment at Guiyang Medical University
The expression of Bax and Bcl-2 mRNA and Bax/Bcl-2 ratio The ratio of Bax:Bcl-2 in the depression, MI and post-MI depression groups was statistically significantly larger than in the sham group (P < 0.05)

Summary

Introduction

There is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear. Bcl-2 is one member of a family of genes which can be divided into two categories according to their effects on apoptosis, one group promoting apoptosis, including Bax, Bak, Bad and Bcl-xS, a second group inhibiting cell death pathways, including Bcl-2 and Bcl-xl [12,13]. Of these proteins, Bcl-2, Bax and Bcl-x are the best characterized genes in the Bcl-2 family [14]. Pro-apoptotic Bax and Bak undergo conformational changes and Bax translocates from cytosol to mitochondria via homo-oligomerization with cell stress signals [15]

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