Sterile and Non-sterile Induction of Neuroinflammation Attenuated by Pre-habilitative Resistance Exercise 2300012

Abstract Introduction Resistance exercise (RE) has been demonstrated to improve cognition in both human and animal studies related to Alzheimer’s Disease (AD). Previous research also suggested that cognitive impairment increases vulnerability to rapid cognitive decline following acute systemic inflammation. However, these mechanisms involved remain poorly understood. This study aimed to investigate how pre-habilitative RE modulates systemic inflammatory responses and its effects on neuroinflammation and cognitive decline. Methods 5-month-old female non-transgenic (nTg) and 3xTg-AD mice were subjected to a five-week RE ladder-climbing regimen prior to either laparotomy under sevoflurane anesthesia or lipopolysaccharide (LPS) injection. Following a three-day recovery period, we evaluated cognition and learning using the novel-object recognition (NOR), Y-maze, and fear-conditioning (FC) tests, focusing on the discrimination index, spontaneous alternation percentage, and freezing behavior. Brain tissue was collected for Western blot (WB) analysis, qPCR, or fixed in neutral-buffered formalin for immunohistochemical assessment. Results In both models of inducing systemic inflammation, RE-trained nTg mice showed significant reductions in pro-inflammatory cytokines, microglial activation, and cognitive deficits compared to sedentary controls. RE-trained 3xTg-AD mice displayed significantly improved discrimination and freezing percentages against their sedentary counterparts, with notable decreases in inflammatory cytokines and apoptotic signaling pathways. This provides compelling evidence that pre-habilitative RE mitigated neuropathologies and cognitive decline in the AD model. Conclusion Pre-habilitative RE can reduce neuroinflammation and cognitive changes induced by both non-sterile and sterile models of systemic inflammation. Furthermore, pre-habilitative RE can ameliorate exacerbation of AD-like phenotype triggered by such acute inflammatory challenges. Funding Source n/a Topic Categories Neuroimmunology (NEUR)