High-intensity interval training and moderate-intensity continuous training alleviate β-amyloid deposition by inhibiting NLRP3 inflammasome activation in APPswe/PS1dE9 mice.

Recent study has demonstrated that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have the same effect to alleviate beta-amyloid pathology in the hippocampus of APPswe/PS1dE9 (APP/PS1) mice. Activation of nucleotide binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is pivotal and has been demonstrated to accelerate beta-amyloid accumulation. The present study aimed to examine whether the exercise-induced beta-amyloid reduction was associated with changes in NLRP3 inflammasome activation. APP/PS1 transgenic mice were randomly assigned to a transgenic sedentary group, HIIT group and MICT group. Nontransgenic littermates were used as wild-type sedentary group. Mice in HIIT and MICT groups were subjected to treadmill exercise for 12 weeks, 5 days/week. The results showed that compared with transgenic sedentary group, beta-amyloid deposition in the hippocampus of HIIT and MICT groups were significantly reduced. Moreover, both HIIT and MICT groups displayed significant increases in the expression of microglial phagocytic receptors triggering receptor expressed on myeloid cells 2, CD36 and scavenger receptor class A compared with transgenic sedentary group. In addition, HIIT and MICT had the same effect to inhibit NLRP3 inflammasome activation, as evidenced by significant reduction in IL-1 beta, active caspase-1p20, NLRP3 and apoptosis-associated speck-like protein containing a caspase activating and recruitment domain (ASC) levels as well as decreased NLRP3/ASC colocalization. These findings indicate that HIIT appears to be an effective intervention as MICT to reduced beta-amyloid deposition by regulating NLRP3 inflammasome-controlled microglial phagocytosis.