Lithium Treatment Improves Cardiac Dysfunction in Rats Deprived of Rapid Eye Movement Sleep.

Abstract

Rapid eye movement (REM) sleep deprivation triggers mania and induces cardiac fibrosis. Beyond neuroprotection, lithium has cardioprotective potential and antifibrotic activity. This study investigated whether lithium improved REM sleep deprivation-induced cardiac dysfunction and evaluated the potential mechanisms. Transthoracic echocardiography, histopathological analysis, and Western blot analysis were performed in control and REM sleep-deprived rats with or without lithium treatment (LiCl of 1 mmol/kg/day administered by oral gavage for 4 weeks) in vivo and in isolated ventricular preparations. The results revealed that REM sleep-deprived rats exhibited impaired contractility and greater fibrosis than control and lithium-treated REM sleep-deprived rats. Western blot analysis showed that REM sleep-deprived hearts had higher expression levels of transforming growth factor beta (TGF-β), phosphorylated Smad 2/3, and alpha-smooth muscle actin than lithium-treated REM sleep-deprived and control hearts. Moreover, lithium-treated REM sleep-deprived hearts had lower expression of angiotensin II type 1 receptor, phosphorylated nuclear factor kappa B p65, calcium release-activated calcium channel protein 1, transient receptor potential canonical (TRPC) 1, and TRPC3 than REM sleep-deprived hearts. The findings suggest that lithium attenuates REM sleep deprivation-induced cardiac fibrogenesis and dysfunction possibly through the downregulation of TGF-β, angiotensin II, and Ca2+ signaling.

• Authors: Pao-Huan Chen, Cheng-Chih Chung, Shuen-Hsin Liu, Yu-Hsun Kao, Yi-Jen Chen
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 19 (Sep 23 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36232526 (Publication Type: Journal Article)

Chemical References

• Actins
• Lithium Compounds
• NF-kappa B
• ORAI1 Protein
• Receptor, Angiotensin, Type 1
• Transforming Growth Factor beta
• Angiotensin II
• Lithium

Topics

• Actins (metabolism)
• Angiotensin II (metabolism)
• Animals
• Heart Diseases
• Lithium (pharmacology, therapeutic use)
• Lithium Compounds
• NF-kappa B (metabolism)
• ORAI1 Protein
• Rats
• Receptor, Angiotensin, Type 1 (metabolism)
• Sleep Deprivation (complications, drug therapy, metabolism)
• Sleep, REM
• Transforming Growth Factor beta (metabolism)