The Role of Exercise in Reducing Hyperlipidemia-Induced Neuronal Damage in Apolipoprotein E-Deficient Mice.

Abstract

Hyperlipidemia causes nervous system-related diseases. Exercise training has developed into an established evidence-based treatment strategy that is beneficial for neuronal injury. This study investigated the effect of exercise on hyperlipidemia-induced neuronal injury in apolipoprotein E-deficient (ApoE−/−) mice. Male ApoE−/− mice (age: 8 weeks) were randomly divided into four groups as follows: mice fed a normal diet (ND), normal diet+swimming training (ND+S), high-fat diet (HD), and high-fat diet+swimming (HD+S). Exercise training consisted of swimming for 40 min/day, 5 days/week for 12 weeks. After 12 weeks, we measured serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c). We also evaluated glial fibrillary acidic protein (GFAP) expression levels using immunohistochemistry, real-time PCR, and immunoblotting. In addition, NLR family pyrin domain-containing 3 (NLRP3), interleukin- (IL-) 18, caspase-1, Bax, Bcl-2, and phosphorylated extracellular signal-regulated kinase (p-ERK) expression levels were measured using immunoblotting. Serum levels of TG, TC, and LDL-c were lower in ApoE−/− HD+S mice than in ApoE−/− HD mice. Immunohistochemistry, real-time PCR, and immunoblotting showed increased levels of GFAP in the ApoE−/− HD group. Immunoblotting revealed increased levels of NLRP3, IL-18, caspase-1, Bax, Bcl-2, and p-ERK in the ApoE−/− HD group; however, they were significantly suppressed in the ApoE−/− HD+S group. Therefore, exercise has protective effects against neuronal injury caused by hyperlipidemia.