Exercise alleviates cisplatin-induced toxicity in the hippocampus of mice by inhibiting neuroinflammation and improving synaptic plasticity.

Chemotherapy-induced cognitive impairment is recognized as the most typical symptom in patients with cancer that occurs during and following the chemotherapy treatment. Recently many studies focused on pharmaceutical strategies to control the chemotherapy side effects, however it is far from satisfactory. There may be a need for more effective treatment options. The aim of this study was to investigate the protective effect of exercise on cisplatin-induced neurotoxicity. Eightweek- old C57BL6 mice were separated into three group: normal control (CON, n = 8); cisplatin injection control (Cis-CON, n = 8); cisplatin with aerobic exercise (Cis-EXE, n = 8). Cisplatin was administered intraperitoneally at a dose of 3.5 mg/kg/day. The Cis-EXE group exercise by treadmill running (14-16 m/min for 45 min daily, 3 times/ week) for 12 weeks. Compared to the CON group, the cisplatin injection groups showed significant decrease in body weight and food intake, indicating successful induction of cisplatin toxicity. The Cis-CON group showed significantly increased levels of pro-inflammatory cytokines including IL-6, IL-1ß, and TNF-α in the hippocampus, while the Cis-EXE group was significantly decreased in the expression of IL- 6, IL-1ß, and TNF-α. In addition, compared to the CON group, the levels of synapserelated proteins including synapsin-1 and -2 were significantly reduced in the Cis- CON group, and there was a significant difference between the Cis-CON and Cis-EXE groups. Antioxidant and apoptosis factors were significantly improved in the Cis-EXE group compared with the Cis-CON group. This study suggest that exercise could be meaningful approach to prevent or improve cisplatin-induced cognitive impairment.

Exercise Training Protects against Atorvastatin-Induced Skeletal Muscle Dysfunction and Mitochondrial Dysfunction in the Skeletal Muscle of Rats.

Statins are used to prevent and treat atherosclerotic cardiovascular disease, but they also induce myopathy and mitochondrial dysfunction. Here, we investigated whether exercise training prevents glucose intolerance, muscle impairment, and mitochondrial dysfunction in the skeletal muscles of Wistar rats treated with atorvastatin (5 mg kg-1 day-1) for 12 weeks. The rats were assigned to the following three groups: the control (CON), atorvastatin-treated (ATO), and ATO plus aerobic exercise training groups (ATO+EXE). The ATO+EXE group exhibited higher glucose tolerance and forelimb strength and lower creatine kinase levels than the other groups. Mitochondrial respiratory and Ca2+ retention capacity was significantly lower in the ATO group than in the other groups, but exercise training protected against atorvastatin-induced impairment in both the soleus and white gastrocnemius muscles. The mitochondrial H2O2 emission rate was relatively higher in the ATO group and lower in the ATO+EXE group, in both the soleus and white gastrocnemius muscles, than in the CON group. In the soleus muscle, the Bcl-2, SOD1, SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. In the white gastrocnemius muscle, the SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. Therefore, exercise training might regulate atorvastatin-induced muscle damage, muscle fatigue, and mitochondrial dysfunction in the skeletal muscles.

Cardiac adaptation to exercise training in health and disease.

The heart is the primary pump that circulates blood through the entire cardiovascular system, serving many important functions in the body. Exercise training provides favorable anatomical and physiological changes that reduce the risk of heart disease and failure. Compared with pathological cardiac hypertrophy, exercise-induced physiological cardiac hypertrophy leads to an improvement in heart function. Exercise-induced cardiac remodeling is associated with gene regulatory mechanisms and cellular signaling pathways underlying cellular, molecular, and metabolic adaptations. Exercise training also promotes mitochondrial biogenesis and oxidative capacity leading to a decrease in cardiovascular disease. In this review, we summarized the exercise-induced adaptation in cardiac structure and function to understand cellular and molecular signaling pathways and mechanisms in preclinical and clinical trials.

Exercise and Neuroinflammation in Health and Disease.

Neuroinflammation is a central pathological feature of several acute and chronic brain diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). It induces microglia activation, mitochondrial dysfunction, the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), pro-inflammatory cytokines, and reactive oxygen species. Exercise, which plays an important role in maintaining and improving brain health, might be a highly effective intervention for preventing neuroinflammation-related diseases. Thus, since exercise can improve the neuroimmune response, we hypothesized that exercise would attenuate neuroinflammation-related diseases. In this review, we will highlight (1) the biological mechanisms that underlie AD, PD, ALS, and MS, including the neuroinflammation pathways associated with microglia activation, NF-κB, pro-inflammatory cytokines, mitochondrial dysfunction, and reactive oxygen species, and (2) the role of exercise in neuroinflammation-related neurodegenerative diseases.

Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms.

Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising due to diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function and calcium regulation. This review summarizes the recent scientific findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

Aerobic Exercise Training Decreases Hepatic Asprosin in Diabetic Rats.

Asprosin, a novel hormone released from white adipose tissue, regulates hepatic glucose metabolism and is pathologically elevated in the presence of insulin resistance. It is unknown whether aerobic exercise training affects asprosin levels in type 1 diabetes mellitus (T1DM). The aim of this study was to determine whether (1) aerobic exercise training could decrease asprosin levels in the liver of streptozotocin (STZ)-induced diabetic rats and (2) the reduction in asprosin levels could induce asprosin-dependent downstream pathways. Five-week-old male Sprague-Dawley rats were randomly divided into control, STZ-induced diabetes (STZ), and STZ with aerobic exercise training groups (n = 6/group). T1DM was induced by a single dose of STZ (65 mg/kg intraperitoneally (i.p.)). The exercise group was made to run on a treadmill for 60 min at a speed of 20 m/min, 4 days per week for 8 weeks. Aerobic exercise training reduced the protein levels of asprosin, PKA, and TGF-ß but increased those of AMPK, Akt, PGC-1ß, and MnSOD. These results suggest that aerobic exercise training affects hepatic asprosin-dependent PKA/TGF-ß and AMPK downstream pathways in T1DM.

Resistance Exercise Training Attenuates the Loss of Endogenous GLP-1 Receptor in the Hypothalamus of Type 2 Diabetic Rats.

The aim of this study was to investigate the effects of resistance exercise training on hypothalamic GLP-1R levels and its related signaling mechanisms in T2DM. The animals were separated into three groups: a non-diabetic control (CON), diabetic control (DM), and diabetic with resistance exercise (DM + EXE) group. The resistance exercise training group performed ladder climbing (eight repetitions, three days per week for 12 weeks). Body weight was slightly lower in the DM + EXE group than the DM group, but difference between the groups was not significant. Food intake and glucose were significantly lower in the DM + EXE group than in the DM group. The blood insulin concentration was significantly higher and glucagon was significantly lower in the DM + EXE group. The DM + EXE group in the hypothalamus showed significant increases in GLP-1R mRNA, protein kinase A (PKA), glucose transporter 2 (GLUT2), and protein kinase B (AKT) and significant decrease in protein kinase C-iota (PKC-iota). Antioxidant enzymes and apoptosis factors were significantly improved in the DM + EXE group compared with the DM group in the hypothalamus. The results suggest that resistance exercise contributes to improvements the overall health of the brain in diabetic conditions.

Aerobic exercise training decreases cereblon and increases AMPK signaling in the skeletal muscle of STZ-induced diabetic rats.

Cereblon (CRBN) has been reported as a negative regulator of adenosine monophosphate-activated protein kinase (AMPK). Aerobic exercise training has been shown to increase AMPK, which resulted in glucose regulation in skeletal muscle. However, the expression level of CRBN and its association with the physiological modulation of glucose are still unclear. Male Sprague-Dawley rats (5-week-old, n = 18) were assigned to control, streptozotocin (STZ, 65 mg/kg)-induced diabetic group, and STZ + exercise (STZ + EXE) group with six rats in each group. Rats in the STZ + EXE group exercised by treadmill running (20 m/min, 60 min, 4 times/week) for 8 weeks. Compared with the STZ group, blood glucose was significantly decreased in the STZ + EXE group. The skeletal muscle of rats in the STZ + EXE group showed a significant decrease in CRBN levels and an increase in AMPK, protein kinase B, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, fibronectin type III domain-containing protein 5, glucose transporter type 4, superoxide dismutase 1, and uncoupling protein 3 levels. These results suggest that CRBN is a potential regulator of glucose homeostasis in the skeletal muscle. Moreover, our results suggest that aerobic exercise training may provide an important physiological treatment for type 1 diabetes by decreasing CRBN and increasing AMPK signaling in skeletal muscle.