Sex Effect on Cardiac Damage in Mice With Experimental Autoimmune Encephalomyelitis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Recent clinical study suggested that MS patient exhibited acute heart failure. Further, 12-lead electrocardiographic study showed a longer QTc interval in both MS patient and experimental autoimmune encephalomyelitis (EAE) Lewis rat. However, there is limited study regarding the effect of sex on cardiac injury in EAE. To our knowledge, sex effect on cardiac damage in mice with EAE has not yet been published. Herein, we examined the role of the immune system in mediating cardiac dysfunction after EAE in female and male mice. Neurological function was subsequently evaluated and cardiac function was assessed by echocardiography at multiple time points after EAE. EAE mice exhibited severe neurological deficit and significant cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 1 and 2 months after EAE induction. Meanwhile male EAE presented increased expression of the oxidative stress (e.g., nicotinamaide adenine dinucleotide phosphate oxidase-2; NOX-2) in heart, as well as cardiac hypertrophy, increased left ventricle (LV) mass and more severe cardiac fibrosis compared with male control mice. In addition, male EAE mice showed significantly increased cardiac canonical inflammatory mediator (e.g., monocyte chemoattractant protein-1; MCP-1, transforming growth factor-β; TGF-β and toll-like receptor 2; TLR-2) compared with female EAE mice at 2 months after EAE induction. In conclusion, EAE increases inflammatory factor expression and aggravates cardiac dysfunction in male mice compared with female mice, which may contribute to different cardiac outcome in EAE mice.

The effect of five weeks of aerobic training with royal jelly consumption on glycemic indices in multiple sclerosis rats

“…Multiple sclerosis (MS) is an inflammatory disease in the central nervous system, and having this disease is associated with metabolic disorders such as obesity (1). Despite the multifactorial nature of MS disease, studies show that weight gain, metabolic disorders, central and peripheral immune system disorders, and axonal demyelination are associated with the incidence of cardiac disorders in MS patients (1,2). Since the central nervous system controls the vessels and internal organs of the body through the sympathetic and parasympathetic system, there seems to be a strong connection between the nervous system and immune cells; because the disorders of the nervous system due to peripheral disruptions can lead to the reaction of the inflammatory system through the increase of free radicals, and by increasing the circulating levels of circulating proinflammatory proteins such as C-reactive protein, interleukin 1 (IL-1), interferon gamma (IFN-γ) lead to damage to the vagus nerves, the adrenergic system, as well as the betaadrenergic receptor (β-AR) (3,4).…”