The present study was undertaken to investigate whether chronic endurance exercise affects tau phosphorylation levels in the brain with Alzheimer's disease (AD)-like pathology. To address this, the transgenic (Tg) mouse model of tauopathies, Tg-NSE/htau23, which expresses human tau23 in the brain, was chosen. Animals were subjected to chronic exercise for 3 months from 16 months of age. The exercised Tg mouse groups were treadmill run at speeds of 12 m/min (intermediate exercise group) or 19 m/min (high exercise group) for 1 hr/day, 5 days/week, during the 3-month period. Chronic endurance exercise in Tg mice increased the expression of Cu/Zn-superoxide dismutase (SOD) and catalase, and also their enzymatic activities in the brain. In parallel, chronic exercise in Tg mice up-regulated the expression of phospho-PKCalpha, phospho-AKT, and phospho-PI3K, and down-regulated the expressions of phospho-PKA, phosphor-p38, phospho-JNK, and phospho-ERK. Moreover, chronic exercise up-regulated both cytosolic and nuclear levels of beta-catenin, and the expression of T-cell factor-4 (Tcf-4) and cyclin D1 in the brain. As a consequence of such changes, the levels of phospho-tau in the brain of Tg mice were markedly decreased after exercise. Immunohistochemical analysis showed an exercised-induced decrease of the phospho-tau levels in the CA3 subregion of the hippocampus. These results suggest that chronic endurance exercise may provide a therapeutic potential to alleviate the tau pathology.

Obesity contributes to systemic inflammation, which is associated with the varied pathogenesis of neurodegenerative diseases. Growing evidence has demonstrated that endurance exercise (EE) mitigates obesity-induced brain inflammation. However, exercise-mediated anti-inflammatory mechanisms remain largely unknown. We investigated how treadmill exercise (TE) reverses obesity-induced brain inflammation, mainly focusing on toll-like receptor-4 (TLR-4)-dependent neuroinflammation in the obese rat brain after 20 weeks of a high-fat diet (HFD). TE in HFD-fed rats resulted in a significant lowering in the homeostasis model assessment of insulin resistance index, the area under the curve for glucose and abdominal visceral fat, and also improved working memory ability in a passive avoidance task relative to sedentary behaviour in HFD-fed rats, with the exception of body weight. More importantly, TE revoked the increase in HFD-induced proinflammatory cytokines (tumour necrosis factor α and interleukin-1β) and cyclooxygenase-2, which is in parallel with a reduction in TLR-4 and its downstream proteins, myeloid differentiation 88 and tumour necrosis factor receptor associated factor 6, and phosphorylation of transforming growth factor β-activated kinase 1, IkBα and nuclear factor-κB. Moreover, TE reduced an indicator of microglia activation, ionised calcium-binding adapter molecule-1, and also decreased glial fibrillary acidic protein, an indicator of gliosis formed by activated astrocytes in the cerebral cortex and the hippocampal dentate gyrus, compared to HFD-fed sedentary rats. Finally, EE up-regulated the expression of anti-apoptotic protein, Bcl-2, and suppressed the expression of pro-apoptotic protein, Bax, in the hippocampus compared to HFD-fed sedentary rats. Taken together, these data suggest that TE may exert neuroprotective effects as a result of mitigating the production of proinflammatory cytokines by inhibiting the TLR4 signalling pathways. The results of the present study suggest that the unique combination of the beneficial effects of TE on the restoration of the blood profile and the anti-inflammatory and anti-apoptotic effects on cognitive function should inspire further investigations into its therapeutic potential for metabolic disorders and neurodegenerative diseases.

BackgroundCurrently, evidence‐based guidelines for salvage therapy to treat mediastinal lymph node (LN) oligo‐recurrence in post‐resection non‐small cell lung cancer (NSCLC) are limited. In patients previously treated by surgery without irradiation, radiotherapy (RT) might be safely utilized. We evaluate the clinical outcomes of salvage RT for patients with LN oligo‐recurrence that developed after radical surgery for NSCLC.MethodsThirty‐one patients with stage I–IIIA NSCLC who developed regional LN oligo‐recurrence between 2008 and 2013 were reviewed. The median time from surgery to recurrence was 12 months. Fifteen patients (48.4%) had single LN recurrence. All patients were irradiated by 3‐dimensional conformal RT at the recurrent LN area with daily fractions of 2–3 Gy, with a median dose of 66 Gy (range 51–66). Sixteen patients also received chemotherapy.ResultsAfter salvage RT, 16 patients achieved a complete response, nine a partial response, and six had stable disease. The median follow‐up was 14 months (range 3–76). One and two‐year in‐field control rates were 88.4% and 75.8%, respectively. One and two‐year progression‐free survival rates were 73.1% and 50.9%, respectively. Progression sites were predominantly distant. Ten of the 31 patients (32.3%) met the revised Response Evaluation Criteria for Solid Tumors for a complete response by the final follow‐up. Recurrent LN size (<3 vs. ≥3 cm) was a significant prognostic factor for progression‐free survival (P = 0.013).ConclusionSalvage RT for patients with regional LN oligo‐recurrence after radical surgery was an effective treatment option with an acceptable level of toxicity.

ASX supplementation enhanced AHN and spatial memory, and a DNA microarray approach provided, for the first time, novel molecular insights into ASX action.

[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.