Markers for Depression in Post-Myocardial Infarction Murine Model

Abstract

Previous research has shown that symptoms of depression are commonly found in patients who suffer from a myocardial infarction (MI). Monoamine transporters such as dopamine, noradrenalin, and serotonin receptors have been shown to have altered levels in depressed patients and are common targets for antidepressants. Other studies have shown that in rats, there is an increase in pro-inflammatory cytokines after experiencing heart failure due to MI. These markers are also commonly associated with depression and other mood disorders. The purpose of this study is to determine if previously identified markers for depression are altered in the brains of mice at multiple time points after acute MI. This study was conducted on B6129SF2/J mice who were randomly assigned to MI or sham coronary artery ligation surgery. Animals were sacrificed at 24 hours (n=10), 4 days (n= 13) or 4 weeks (n= 13) after surgery. Whole cerebral hemispheres were collected and bisected from the 4 day and 4 week groups. One hemisphere was homogenized and total protein extracted. The 24 hour group had cerebral cortical and subcortical structures collected separately, with tissue from one hemisphere used for total protein extraction. Western blotting was used to determine expression levels of proteins of interest. Receptors for neurotransmitters linked to depression (serotonin and dopamine) were examined along with pro-inflammatory cytokines (inducible nitric oxide synthase (iNOS), neural cell adhesion molecule (NCAM), and nuclear factor kappa-beta (NF-kB) protein). Imaging was done through Image Studio software, and T-tests determined if significant differences were found among the MI and sham groups at each of the different time points. No consistent differences were found in inflammatory and monoamine receptor expression in mice brain tissue in sham vs myocardial infarction animals at any time point. NF-kB was significantly reduced at 4 days after injury (p = 0.05). D3 expression was increased in the subcortex, 24 hours after injury (p = 0.047). No clear effect of MI on markers associated with depression was detected in this study. It is likely that any changes that might occur are time dependent, and more time points, especially longer-term, should be utilized in future studies. Any changes may also be restricted to certain cerebral structures, necessitating finer dissection of areas to be studied.