Title : Between the brain and the heart: Effects of reward system activation on the recovery process following myocardial infarction
Abstract:
Background: Epidemiological data show a correlation between negative emotional states, such as depression and stress, to a higher incidence of acute cardiovascular events like myocardial infarction (MI), with more frequently occurring comorbidities and mortality. Consistently, practices promoting a positive emotional state, including meditation and stress reduction, were correlated with cardiovascular health and reduced rates of hospitalization and mortality following MI. However, it remains unknown how the emotional state influences the recovery process following MI. While some patients regain much of their cardiac function and maintain good overall health, others will go on to develop complications, such as heart failure. Here, we choose to focus on a specific neuronal network, the reward system, which mediates positive-valanced emotions, motivation, and expectation. We test whether and how activation of ventral tegmental area (VTA), a main component of the reward system, affects recovery following MI. Methods: we use designer receptor exclusively activated by designer drugs (DREADDs), functional cardiac magnetic resonance (CMR),histology, immunofluorescence, enzyme linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), endothelial tube formation assay, full proteomic analysis, pseudorabies neuronal tracing.
Results: VTA activation in mice enhanced recovery following MI and attenuated the decrease in cardiac function that is normally observed. VTA activation reduced the area occupied by non-contractile scar tissue and amplified cardiac vascularization. Proteomic analysis revealed that reward system activation induced a systemic response, including complement activation and metabolic processes that were previously correlated with a favorable recovery outcome.We established anatomical connection between the VTA and the liver and show reduced sympathetic tone to the liver in VTA activated mice. Endothelial tube formation was enhanced by treatment with liver proteins. Conclusion: Collectively, our data suggest that reward-system activation results in better cardiac function and fibrosis following MI. Proteomics highlight changes in immune system function along with alterations in hepatic protein production, as seen in C3. An anatomical connection was also identified between the VTA and the liver. Liver-produced proteins in VTA-activated mice enhance angiogenesis in-vitro, which was also evident in cardiac tissue in vivo.
