Therapeutic Potentials of Lithium on Cardiac Metabolism, Apoptosis and Structural Remodeling in REM Sleep Deprived-Rats with Manic-Like Behaviors

Project: A - Government Institutionb - National Science and Technology Council

Project Details

Description

Heart failure is the principal cause of sudden cardiac death in the population of bipolar disorder. Our previous clinical studies illustrated that lithium treatment was associated with favorable cardiac function and geometric pattern in individuals with bipolar disorder. However, mechanisms underlying lithium’s actions on cardiac remodeling remain unclear. Over the decades, rapid-eye movement (REM) sleep deprivation model has been established to induce manic-like behaviors and cardiac diseases in rodents. By using this animal model, our in vivo study discovered that REM sleep deprived rats exhibited myocardial hypertrophy and hyaline degeneration over the subendocardium of ventricular wall (the pathology characterizing disturbed energy metabolism and mitochondrial dysfunction). Lithium at low therapeutic level (plasma concentration of 0.36 ± 0.03 mM) alleviated these pathologies in REM sleep-deprived hearts. Furthermore, by adopting H9c2 cellular model, our in vitro study demonstrated that lithium treatment at 0.3 mM downregulated mitochondrial fatty acid oxidation in H9c2 cardiomyocytes through the regulation of glycogen synthase kinase-3 beta/acetyl-CoA carboxylase 2 signaling pathway. The findings suggest that lithium has cardioprotective effects by directly modulating mitochondrial fatty acid utilization in cardiomyocytes at low therapeutic concentrations.
StatusFinished
Effective start/end date8/1/227/31/23

Keywords

  • lithium
  • cardioprotection
  • rapid-eye-movement sleep deprivation
  • mania
  • catecholamine
  • cardiac metabolism
  • cardiac strain
  • color Doppler myocardial image
  • pathway enrichment analysis

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