Joon Yong Cho

Neuroprotective effects of treadmill exercise on BDNF and PI3-K/Akt signaling pathway in the cortex of transgenic mice model of Alzheimer's disease.

(AD). Although physical exercise and AD have received attention in the scientific literature, the mechanism through which treadmill exercise may impact the brain insulin signaling of AD has not been elucidated. This study aimed to evaluate the neuroprotective effects of treadmill exercise on apoptotic factors (Bcl-2/Bax ratio, caspase-3), HSP70, COX-2, BDNF and PI3-K/Akt signaling pathway in the cortex of NSE/hPS2m transgenic mice model of AD. Treadmill exercise ameliorated cognitive function in water maze test and significantly increased the level of Bcl-2/Bax ratio and HSP-70 in Tg-exe group compared to Tg-con group; on the other hand, it significantly decreased the expression of caspase-3 and COX-2 in Tg-exe group compared to Tg-con group. In addition, treadmill exercise significantly increased the expression of BDNF and PI3K/Akt in Tg-exe group compared to Tg-con group. Consequently, treadmill exercise improves cognitive function possibly via activating neurotrophic factor, BDNF and PI3k/Akt signaling pathway, and Aβ-induced neuronal cell death in the cortex of Tg mice was markedly suppressed following treadmill exercise. These results suggest that treadmill exercise may be beneficial in preventing or treating Alzheimer’s disease.

Astaxanthin supplementation enhances adult hippocampal neurogenesis and spatial memory in mice

SCOPE There is a growing necessity for efficacious natural supplements with antioxidant effects on the brain, in particular, hippocampal function. One such compound, which also has a neuroprotective effect, is the carotenoid astaxanthin (ASX). Despite ASXs potential benefit to the brain, very little is known about its effect on hippocampal plasticity and cognition. Thus, we investigated the effect of ASX on adult hippocampal neurogenesis (AHN) and spatial memory using a mouse model. METHODS AND RESULTS Dose-response was examined in mice fed ASX-supplemented diets (0, 0.02, 0.1, and 0.5%) to define the effect of ASX on AHN. In conjunction with AHN results, hippocampus-dependent cognitive function was assessed. We delineated molecular mechanisms associated with ASX-enhanced AHN using DNA microarray analysis. Results revealed that ASX enhanced cell proliferation and survival at 0.1% and 0.5% doses. Newborn mature neurons were higher only with 0.5% ASX, which also enhanced spatial memory. Transcriptomic profiling revealed potential AHN-associated molecules (Prl, Itga4, and Il4) that were ASX induced. Their downstream factors, identified through Ingenuity Pathway Analysis, were positively correlated with ASX-induced increases in spatial memory. CONCLUSION ASX supplementation enhanced AHN and spatial memory, and a DNA microarray approach provided, for the first time, novel molecular insights into ASX action.

Effects of treadmill exercise on brain insulin signaling and β-amyloid in intracerebroventricular streptozotocin induced-memory impairment in rats

[Purpose] The purpose of the study is to explore effect of 6 weeks treadmill exercise on brain insulin signaling and β-amyloid(Aβ). [Methods] The rat model of Alzheimer’s disease(AD) used in the present study was induced by the intracerebroventricular(ICV) streptozotocin(STZ). To produce the model of animal with AD, STZ(1.5mg/kg) was injected to a cerebral ventricle of both cerebrums of Sprague-Dawley rat(20 weeks). The experimental animals were divided into ICV-Sham(n=7), ICV-STZ CON(n=7), ICV-STZ EXE(n=7). Treadmill exercise was done for 30 min a day, 5 days a week for 6 weeks. Passive avoidance task was carried out before and after treadmill exercise. [Results] The results of this study show that treadmill exercise activated Protein kinase B(AKT)/ Glycogen synthase kinase 3α (GSK3α), possibly via activation of insulin receptor(IR) and insulin receptor substrate(IRS) and reduced Aβ in the brain of ICV-STZ rats. More interestingly, treadmill exercise improved cognitive function of ICV-STZ rats. Finally, physical exercise or physical activity gave positive influences on brain insulin signaling pathway. [Conclusion] Therefore, treadmill exercise can be applied to improve AD as preventive and therapeutic method.

The effect of treadmill exercise on inflammatory responses in rat model of streptozotocin-induced experimental dementia of Alzheimer's type.

[Purpose] The aim of this study was to investigate the effect of treadmill exercise on inflammatory response in streptozotocin (STZ)-induced animal model of Alzheimer’s disease (AD). [Methods] To induce the animal model of AD, Sprague-Dawley rats were injected into intracerebroventricular (ICV) injection with 1.5 mg/kg of STZ. Rats were divided into three groups as Sham-con group (n = 7), STZ-con group (n = 7) and STZ-exe group (n = 7). Exercise group ran on the treadmill for 30 min/day, 5 days/week during 6 weeks. [Results] The results of this study were as follows: First, STZ-exe group was improved on cognitive function when compared to STZ-con group in water maze test. Second, STZ-exe group help reduce the expression level of amyloid-beta (Aβ). In addition, Toll-like receptors-4 (TLR4), Nuclear factor-kB (NF-kB), Tumor necrosis factor-α (TNF-α) and Interleukin-1α (IL-1α) level of STZ-exe group was significantly decreased when compared to STZ-con group. [Conclusion] These results show that treadmill exercise had positive effect on cognitive function and reduced inflammatory response in STZ-induced animal model of AD.

Maternal exercise reduces hyperthermia-induced apoptosis in developing mouse brain

Purpose: Hyperthermia-induced apoptosis is mediated by mitochondrial pathway, and is temporally correlated with alterations in mitochondrial morphology in neuroepithelial cells. In addition, regular exercise up-regulates heat shock proteins (HSPs) that inhibit apoptosis. However, embryo-protective effects of maternal exercise against heat exposure during pregnancy have not been fully understood yet. Materials and methods: To investigate the role of maternal exercise in protecting embryos from hyperthermia, we measured apoptosis-related factors and HSPs in Hsp70 knockout mouse embryos. Pregnant mice were divided into control, exercise, hyperthermia-after-exercise, and hyperthermia groups. Where appropriate the swimming exercise was performed for 5–10 min/day from embryonic day (ED) 1 to ED 8, and hyperthermia (43°C, 5 min) was induced on ED 8. To characterise the effects of maternal exercise on apoptosis-related factors and HSPs, we performed western blotting and transmission electron microscopy. Results: Caspase-9, -7, -3 and Bax were down-regulated in the hyperthermia-after-exercise group and Bcl-2, Hsp27 and Hsp110 were up-regulated. The number of apoptotic cells was markedly reduced in the hyperthermia-after-exercise group. Conclusions: Maternal exercise plays an important role in inhibiting apoptotic cell death in embryos against hyperthermic exposure during pregnancy.

Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity induced by a high-fat diet

[Purpose] This study aimed to investigate the effects of treadmill exercise on body weight, blood biochemistry, and autophagy. [Methods] Triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, insulin, and glucose levels were measured, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated, and the soleus muscle was analyzed for autophagy-related factors (Beclin-1, p62, LC3, Lamp-2) in rats with obesity induced by a high-fat diet. Eight-week-old Sprague Dawley rats were fed a high-fat diet for 35 weeks and then subjected to 10 weeks of treadmill exercise. The experimental group was divided into a Normal Diet-Sedentary (ND-SED, n=8) group, an (High-Fat Diet-Sedentary (HF-SED, n=8) group, and an High-Fat Diet + Treadmill Exercise (HF-TE, n=8) group. The intensity of treadmill exercise was set as 8 m/min for 5 min, 11 m/min for 5 min, 15 m/min for 20 min, and 11 m/min for the last 5 minutes. A glucose tolerance test was performed at the 2nd and 8th week of exercise by sampling of tail blood. [Results] With endurance exercise, the HFTE group showed a significant decrease in body weight, with improved blood biochemical indices and HOMA-IR scores, in comparison with the HF-SED group. However, there was no significant difference in Beclin-1, p62, LC3, and Lamp-2 proteins as measured by autophagic flux in the soleus muscle. [Conclusion] Treadmill exercise induced improvements in body weight, body fat, and biochemical indicators of obesity and Type 2 diabetes, but had no effect on autophagy in soleus muscle.