PENG-based self-powered transcutaneous auricular vagus nerve stimulation attenuated myocardial infarction-induced heart-brain remodeling via ameliorating the neuroinflammatory response in central amygdala.

BACKGROUND

Myocardial infarction (MI) is responsible for the majority of deaths worldwide and depression can intensify the detrimental cycle of heart-brain remodeling after MI. Transcutaneous auricular vagus nerve stimulation (taVNS) is an effective non-invasive neuromodulation strategy for treating depression and cardiovascular disease (CVD). Piezoelectric nanogenerators (PENGs) can convert the mechanical energy of organism into electrical energy to achieve self-powering. Self-powered vagal neuromodulation based on PENGs have been used for neural stimulation and CVD treatment. We aim to determine the interaction between heart and central amygdala (CeA), integrate self-powered PENG technology into taVNS system and explore the effects and underlying mechanisms of taVNS on heart-CeA remodeling after MI.

METHODS

Neural tracing and chemogenetic technologies were used to confirm the heart-CeA connectivity. A four-weeks taVNS treatment was promoted after MI induction in male Sprague-Dawley rats. Then, depression-like behaviors and cardiac remodeling were evaluated. Besides, neuronal activity and neuroinflammation levels were assessed and the underlying mechanisms were elucidated. The self-powered PENG technology was integrated into the taVNS system and its neuromodulation effectiveness was evaluated.

RESULTS

MI increased neuronal activity in the CeA and depression-like behaviors, and over-activation of the CeA led to cardiac dysfunction, resulting in malignant feedback. taVNS attenuated MI-induced "heart-CeA" remodeling, improved cardiac function, and reduced depression-like behaviors by ameliorating the neuroinflammatory response via MLCK pathway in the CeA. In addition, the self-powered PENG-based system enabled effective transcutaneous neuromodulation.

CONCLUSION

PENG-based self-powered taVNS holds potential for heart-brain neuromodulation, offering a synergistic strategy for treating cardiac and mental co-morbidities after MI.