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.