Supporting data for "Investigating the neuroprotective effects of resistance exercise on Alzheimer’s disease and acute systemic inflammatory challenge."

Alzheimer’s Disease (AD) is considered a multifactorial neurodegenerative disease as more than 90% of all AD cases are sporadic and without a clear pattern of genetic inheritance. Currently, there are no effective therapeutics to cure AD, and available drugs only aim to slow disease progression and provide symptomatic relief for patients. Physical exercise has long been recognized for its benefits to overall health, and numerous studies have shown that physical exercise improves cognition in older adults and cognitively impaired patients. However, resistance-type regimes remain poorly investigated. Ladder-based resistance exercise paradigm was established in two transgenic AD mouse models, 3×Tg-AD and 5×FAD, and was demonstrated to improve cognitive functions and reduce neuropathological markers such as mRNA expression of pro-inflammatory cytokines, tau hyperphosphorylation, and glial cell activation. Notably, an increase in muscle strength and expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α) was only observed in 3×Tg-AD mice. The duration of resistance exercise was determined to be a crucial factor, as ten weeks did not yield the same neurological benefits as five weeks in 3×Tg-AD mice. Acute systemic activation of the immune system can negatively modulate the central nervous system, and the lack of exercise capacity is one of the factors associated with poor cognitive performance after acute surgical trauma and infection in patients. Furthermore, pre-existing cognitive impairment may impart susceptibility to accelerated cognitive decline following an acute systemic inflammatory episode. Given that resistance exercise can modulate the expression of inflammatory mediators in the brain and the periphery, its role as a potential prophylactic intervention against sterile and non-sterile systemic inflammatory challenges was examined using the experimental models of laparotomy under sevoflurane anesthesia and peripheral administration of lipopolysaccharide (LPS) in non-transgenic and 3×Tg-AD mice. In non-transgenic mice, the preconditioning with five weeks of resistance exercise reduced systemic and neuroinflammation and improved cognitive outcomes in the puzzle test compared to untrained mice after surgery or infection. The preconditioning of 3×Tg-AD mice with resistance exercise mitigated the heightened neuroinflammation and exacerbated cognitive decline caused by surgery or infection. These findings suggest resistance exercise as a therapeutic strategy for pre-existing cognitive impairment and a potent prophylactic against anti-inflammatory systemic inflammatory challenges.

阿尔茨海默病（Alzheimer’s Disease，AD）被视为一种多因素神经退行性疾病，因为超过90%的AD病例为散发性，且无明确的遗传遗传模式。目前，尚无有效的治疗方法可治愈AD，现有的药物仅旨在减缓疾病进程并为患者提供症状缓解。长期以来，体育锻炼对整体健康的益处已被广泛认可，众多研究表明，体育锻炼可改善老年人的认知能力和认知障碍患者的认知功能。然而，抗阻运动方案的研究尚不充分。在两种转基因AD小鼠模型3×Tg-AD和5×FAD中建立了基于阶梯的抗阻运动范式，并证实其能改善认知功能并降低神经病理学标志物，如促炎细胞因子的mRNA表达、tau蛋白过度磷酸化和胶质细胞激活。值得注意的是，仅在3×Tg-AD小鼠中观察到肌肉力量和过氧化物酶体增殖物激活受体γ共激活因子（PGC1-α）的表达增加。抗阻运动的持续时间被确定为关键因素，因为在3×Tg-AD小鼠中，十周的运动并未产生与五周相同的神经学益处。急性全身性免疫系统激活可以负向调节中枢神经系统，而缺乏运动能力是患者急性手术创伤和感染后认知表现不佳的相关因素之一。此外，现有的认知障碍可能使患者在急性全身性炎症事件后加速认知衰退。鉴于抗阻运动可以调节大脑和周围组织中的炎症介质表达，本研究利用开腹手术下吸入七氟烷麻醉和向非转基因及3×Tg-AD小鼠周围注射脂多糖（LPS）的实验模型，探讨了抗阻运动在潜在预防无菌性和非无菌性全身性炎症挑战中的作用。在非转基因小鼠中，五周的抗阻运动预处理减少了全身性和神经炎症，并在手术或感染后与未训练小鼠相比，在迷津测试中改善了认知结果。3×Tg-AD小鼠的抗阻运动预处理减轻了手术或感染引起的神经炎症加剧和认知衰退。这些发现表明，抗阻运动是治疗现有认知障碍的有效策略，也是对抗炎症性全身性炎症挑战的有效预防措施。