Abstract

Introduction: Heart failure patients have a significant depression risk, with two-to-three-times higher possibility compared to the general population (Rustad et al., 2013). Diminished cerebral oxygen supply from reduced perfusion in heart failure may play a role in the development of mood disorders (Mueller et al., 2020). Suffering from both conditions increases hospitalization and mortality rates compared to patients without depression (Celano & Huffman, 2018). New research is needed for better patient outcomes. Previous murine studies induce cardiac impairments acutely (Frey et al. 2014). However, progressively induced heart failure studies assessing behavior over time are lacking.

Objectives: The aims of this study were: 1) to identify specific timepoints where cardiac phenotypes became more pronounced and, 2) to establish a clear link between the severity of cardiac impairments and the expression of depressive symptoms.

Methods: The plan was to gradually induce heart failure using viral vectors to modify the cardiomyocyte circadian clock through the removal of the clock gene brain and muscle ARNT-Like 1 (Bmal1) (Young et al. 2014). Cardiac and behavioral phenotypes were assessed using heart function and behavior tests.

Results: Immunoblotting analysis revealed no difference in BMAL1 protein levels in control and knockout animals. Consistent with the inability to cause heart failure, cardiac and behavioral phenotypes tested were not significantly different between control and experimental groups over time (p > 0.05).

Conclusion: The heart-brain relationship remains an important research topic. Future experiments should test viral vectors efficiency at larger concentrations and measure differences in BMAL1 protein expression in heart tissue.