Long-term exercise training inhibits inflammation by suppressing hippocampal NLRP3 in APP/PS1 mice

Abstract

Behavioral experiments have demonstrated that long-term physical exercise can be beneficial for learning and memory dysfunction caused by neuroinflammation in Alzheimer's disease (AD). However, the molecular mechanism remains poorly understood due to a lack of sufficient pertinent biochemical evidence. We investigated the potential effect of long-term physical exercise on cognition and hippocampal gene and protein expression changes in a transgenic AD mouse model. Following twenty weeks of treadmill exercise, transgenic AD mice showed improvement in cognitive functions and downregulation of Nod-like receptor protein 3 (NLRP3) (p ​< ​0.01), interleukin-1beta (IL-1β) (p ​< ​0.05), and amyloid-β1-42 (Aβ1-42) (p ​< ​0.05) expression levels. In addition, we observed significant reductions of microglial activation and hippocampal neuronal damage in the exercised AD mice (p ​< ​0.01), which might be a result of the downregulation of NLRP3-mediated signaling and neuro-inflammatory responses. As neuronal damage due to inflammation might be a likely cause of AD-associated cognitive dysfunction. Our results suggested that the anti-inflammatory effects of exercise training involved downregulating the expression of key inflammatory factors and might play an important role in protecting hippocampal neurons against damage during the course of AD.

Keywords

• Exercise
• NLRP3
• Neuroinflammation
• Hippocampus
• APP/PS1 mice
• Alzheimer's