Recent studies have suggested that exercise may be beneficial for delaying or attenuating Alzheimer’s disease (AD). However, the underlying mechanisms were not clear. Microglia-mediated neuroinflammation is suggested to play an important role in the pathology of AD. The present study investigated the beneficial effects of treadmill exercise on amyloid-β (Aβ) deposition and cognitive function in amyloid precursor protein (APP)/PS1 mice in the early stage of AD progression and microglia-mediated neuroinflammation was mainly analyzed. The results demonstrated that 12 weeks of treadmill exercise preserved hippocampal cognitive function in APP/PS1 mice and substantially suppressed Aβ accumulation in the hippocampus. Treadmill exercise significantly inhibited neuroinflammation, which was characterized by a remarkably reduced expression of pro-inflammatory factors and increased expression of anti-inflammatory mediators in the hippocampus, resulting from a shift in activated microglia from the M1 to M2 phenotype. Treadmill exercise also attenuated oxidative stress presented by a marked reduction in methane dicarboxylic aldehyde (MDA) level and dramatically elevated SOD and Mn-SOD activities in the hippocampus. These findings suggest that treadmill exercise can effectively prevent the decrease in hippocampal-dependent cognitive function and Aβ deposits in early AD progression possibly via modulating microglia-mediated neuroinflammation and oxidative stress.

Background: Whether exercise prevents fall-related injuries in different health conditions and with different training protocols is still unclear. This study aimed to determine the effect of exercise on fall-related injuries by participant characteristics and divergent exercise protocols. The safety and compliance of exercise were also examined. Methods: Electronic database searches were conducted in PubMed, Web of Science, and EMBASE for randomised controlled trials that evaluated the influence of exercise on fall-induced injuries in older people. Results: Twenty-five trials met the inclusion criteria. Exercise significantly reduced the risk of fall-related injuries in older adults, risk ratio (RR) 0.879 [95% confidence interval (CI) 0.832-0.928]. Among the injuries, events needing medical care or resulting fractures were also decreased by exercise intervention, with RR 0.681 (0.562-0.825) and 0.561 (0.366-0.860), respectively. When analysis was stratified by participant characteristics and exercise protocols, we found that participants at high risk of falling, or with osteoporosis, were sensitive to exercise intervention. Combined exercise protocols and balance training were the most effective exercise types in reducing fall-related injuries. Exercise-associated beneficial effects were even significant in very old people (≥80 years) and across the duration of interventions (< 6 months, 6 to 12 months and ≥ 12 months). Exercise only generated a very low injury rate per participant year (0.002, 95% CI 0-0.05) and showed relatively good compliance of exercise (as reported in the included papers) (78.5, 95% CI 72.8-84.2%). Conclusions: Exercise is effective in preventing fall-induced injuries across a variety of baseline participant characteristics and exercise protocols. Exercise was associated with a low injury rate and had a good compliance, suggesting it is a feasible approach to managing fall-related injuries.

Background The bone formation ability of type 2 diabetes is inhibited, and exercise can effectively improve the bone formation of T2DM. However, whether exercise can mediate the Wnt3a/β-catenin pathway to improve the mechanism of bone formation and metabolism still needs further research. Methods A T2DM mouse model was established by a high-fat diet and STZ injection, and the mice were trained with swimming and downhill running exercise. Alizarin red staining is used to observe the changes of the left femoral trabecular bone; micro-CT is used to analyze the trabecular and cortical BMD, BV/TV, BS/BV, BS/TV, Tb.Th, Tb.Sp; the ALP staining of skull was used to observe the changes in ALP activity of bone tissues at the skull herringbone sutures; ALP staining was performed to observe the changes in the number of OBs and ALP activity produced by differentiation; Quantitative PCR was used to detect mRNA expression; Western blot was used to detect protein expression levels. Results When the Wnt3a/β-catenin pathway in the bones of T2DM mice was inhibited, the bone formation ability of the mice was significantly reduced, resulting in the degradation of the bone tissue morphology and structure. Swimming caused the significant increase in body weight and Runx2 mRNA expression, while downhill running could significantly decrease the body weight of the mice, while the tibia length, wet weight, and the trabecular morphological structure of the distal femur and the indexes of bone histomorphology were significantly improved by activating the Wnt3a/β-catenin pathway. Conclusions Bone formation is inhibited in T2DM mice, leading to osteoporosis. Downhill running activates the Wnt3a/β-catenin pathway in the bones of T2DM mice, promotes OB differentiation and osteogenic capacity, enhances bone formation metabolism, and improves the bone morphological structure.

No abstract

Background Meg3 has been shown to attenuate T2DM bone autophagy by activating p62 to inhibit bone formation. However, whether exercise can reverse this process to promote T2DM bone formation and its mechanism remains unknown. Methods A T2DM mouse model was established by a high-fat diet and STZ injection, and the mice were trained with 8-week HIIT and downhill running exercise. Micro-CT was used to scan the bone microstructure. Bone morphology was observed by HE staining, and the osteoblast (OB) activity in bones was observed by AKP staining. Calcium ion and phosphorus concentration in serum was detected by ELISA; RT-PCR was used to detect the mRNA level, and Western blot was used to detect the protein level of related indexes in Meg3/p62/Runx2 pathway. Results The inhibition of bone autophagy, in the bones of T2DM mice, resulted in the degradation of the bone tissue morphology and structure, with the increase of the expressions of Meg3, PI3K, Akt, mTOR, p62 and NF-κB. However, 8-week HIIT and downhill running could reverse this process, especially downhill running, manifested with the up-regulation of miR-16 mRNA level, along with Beclin-1, LC3 II and Runx2 mRNA and protein level. Conclusion T2DM leads to pathology in model mice. Eight-week HIIT and downhill running exercise can inhibit Meg3, activate autophagy of osteoblasts and promote bone formation in T2DM mice.