Exercise‐Induced Alterations in TrkB expression in the 5XFAD Mouse Model of Alzheimer’s Disease

Alzheimer's Disease (AD) is a slow progressing neurodegenerative disease with various environmental and endogenous factors implicated in its development. Two such factors include downregulation of tropomyosin receptor kinase B (TrkB) and its ligand, brain derived neurotrophic factor (BDNF), which normally facilitate the function and survival of neurons. While the exact causes of AD are still unknown, studies have shown that interventions such as aerobic exercise may reduce the risk of its progression. Interestingly, BDNF and TrkB each have unique expression patterns in the presence Aβ plaques and tau tangles, the main pathologies of AD; these patterns further fluctuate across different exercise types, intensities, and durations.In the current study, we used the 5XFAD mouse model of AD (36 weeks of age) to investigate the nature of exercise-induced neurotrophin alterations. We compared transgenic mice (Tg) and their wild-type (WT) littermates following an exercise regimen consisting of a 60-minute/day steady-state treadmill exercise protocol for 3 weeks. We used immunofluorescent staining to examine the cortical expression of BDNF and TrkB across these groups.We found similar levels of TrkB expression in both exercised groups (WT and Tg) but significantly lower TrkB expression in the exercised 5XFAD Tg mice compared to their sedentary littermates. We failed to observe changes in BDNF expression across any of the groups.The ability of exercise to restore TrkB protein levels in 5XFAD Tg mice to those of exercised wildtype littermates, suggests that TrkB may be considered a potential target for therapeutic intervention. We further postulate that exercise may have a restorative function on cognition and thus may be a prospective therapeutic avenue of treatment for AD and associated cognitive disorders.