Effects of Exercise Training on Anxious-Depressive-like Behavior in Alzheimer Rat

Purpose This study aimed to examine the effects of treadmill training on anxious-depressive-like behaviors of transgenic Alzheimer rats in the early stage of Alzheimer's disease (AD) and provided evidence of exercise in alleviating fear-avoidance behavior deficits. Methods Male 2-month-old TgF344-AD and wild-type rats were divided into wild-type (n= 9), AD (n= 8), and AD + treadmill exercise (Exe) groups (n= 12). After 8 months of exercise, the passive avoidance test, Barnes maze task, novel object recognition test, and object location test were used to measure learning and memory function. The open-field test, elevated plus maze, sucrose preference test, and forced swim test were conducted to determine the anxious-depressive-like behavior of AD rats. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay analysis, and related assay kits were used to measure inflammatory cytokines, oxidative stress, amyloid-beta production, and tau hyperphosphorylation. Results Behavioral tests revealed that 12-month-old animals did not show any spatial learning and memory deficits but did display anxious-depressive-like behavior (open field, center time:P= 0.008; center entries:P= 0.009; line crossings:P= 0.001). However, long-term exercise significantly inhibited anxious-depressive-like behavior in AD rats (center time:P= 0.016; center entries:P= 0.004; line crossings:P= 0.033). In addition, these animals displayed increased amyloid-beta deposition, tau hyperphosphorylation, microgliosis, inflammatory cytokines release, and oxidative damage, which were attenuated significantly by long-term exercise training. Conclusion Long-term exercise training alleviated anxious-depressive-like behavior and improved fear-avoidance behavior in transgenic AD rats, supporting exercise training as an effective approach to prevent anxiety, depression, and fear-avoidance behavior deficits in the early stages of AD pathogenesis.