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

Abstract

Recent study has demonstrated that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have the same effect to alleviate β-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 β-amyloid accumulation. The present study aimed to examine whether the exercise-induced β-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, β-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-1β, 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 β-amyloid deposition by regulating NLRP3 inflammasome-controlled microglial phagocytosis.

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

“…Data from the literature indicate a positive role of physical exercise in the suppression of NLRP3. Studies on animal models indicate that physical activity prevents Aβ-induced disturbances in the NLRP3 inflammasome pathway in the hippocampus of mice as well as reduces β-amyloid deposition by regulating NLRP3 inflammasome-controlled microglial phagocytosis [ 161 , 162 ]. In addition, a low-calorie diet may also upregulate pathways that inhibit NLRP3 activation [ 163 ].…”

Exercise Inhibits NLRP3 Inflammasome Activation in Obese Mice via the Anti-Inflammatory Effect of Meteorin-like

“…Consistent with this notion, individualized exercise prescription has been reported to attenuate ASC gene expression in peripheral blood cells in obese individuals [ 38 ]. Animal studies have also shown that exercise suppresses NLRP3 inflammasome signaling in the aorta of obese mice [ 39 ], diabetic cardiomyopathy [ 40 , 41 ], and various brain regions, including the hippocampus [ 42 ], thus exerting protective effects against disease progression. However, the impact of exercise on adipose tissue NLRP3 inflammasome, as well as underlying mechanisms, remains poorly understood.…”

Microglia Polarization in Alzheimer’s Disease: Mechanisms and a Potential Therapeutic Target

“…Recent studies showed that Aβ-induced pro-inflammatory factors such as IL-6 and TNF-α were possibly medicated by thioredoxin-interacting protein (TXNIP)/thioredoxin (TRX)/NOD-like receptor pyrin domain-containing protein 3 (NLRP3) pathway in microglial cells ( Feng and Zhang, 2019 ; Figure 2 ). Moreover, Aβ could induce the activation of NLRP3 inflammasome in microglia, contributing to the activation of microglia toward M1 polarization ( Halle et al, 2008 ; Liang et al, 2020 ; Zhang et al, 2020 ). Another study showed that Aβ led to the enhancement of pro-inflammatory cytokines such as IL-1β and IL-6 via regulating the homeostasis of ornithine decarboxylase and antizyme ( Cheng et al, 2019 ).…”