Exercise reduces cognitive aging, neurodegeneration, and Alzheimer's disease (AD) risk. Acute exercise reduces the activity of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limi Show more
Exercise reduces cognitive aging, neurodegeneration, and Alzheimer's disease (AD) risk. Acute exercise reduces the activity of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme in the production of Aβ. However, mechanisms mediating these effects remain largely unknown. Work has implicated brain-derived neurotrophic factor (BDNF) in the processing of amyloid precursor protein (APP). BDNF is an exercise-induced neurotrophin known for its role in synaptic plasticity, neurite growth, and neuronal survival. Previously, our lab has shown using an ex vivo model that treatment of the prefrontal cortex with BDNF reduced BACE1 activity, highlighting a BDNF to BACE1 link. The purpose of this research was to examine whether BDNF treatments resulted in similar biochemical adaptations to APP processing as exercise training. Male C57BL6/J mice were assigned into one of four groups ( Show less
Exercise has been shown to be beneficial for individuals with Alzheimer's disease (AD). In rodent models of AD, exercise decreases the amyloidogenic processing of the amyloid precursor protein (APP). Show more
Exercise has been shown to be beneficial for individuals with Alzheimer's disease (AD). In rodent models of AD, exercise decreases the amyloidogenic processing of the amyloid precursor protein (APP). Although it remains unclear as to how exercise is promoting this shift away from pathological APP processing, there is emerging evidence that exercise-induced factors released from peripheral tissues may facilitate these alterations in brain APP processing. Interleukin-6 (IL-6) is released from multiple organs into peripheral circulation during exercise and is among the most characterized exerkines. The purpose of this study is to examine whether acute IL-6 can modulate key enzymes responsible for APP processing, namely, a disintegrin and metalloproteinase 10 (ADAM10) and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which initiate the nonamyloidogenic and amyloidogenic cascades, respectively. Male 10-wk-old C57BL/6J mice underwent acute treadmill exercise bout or were injected with either IL-6 or a PBS control 15 min prior to tissue collection. ADAM10 and BACE1 enzyme activity, mRNA, and protein expression, as well as downstream markers of both cascades, including soluble APPα (sAPPα) and soluble APPβ (sAPPβ), were examined. Exercise increased circulating IL-6 and brain IL-6 signaling (pSTAT3 and Show less