Long-term Exercise Training Prevents Anxious-depressive-like Behavior In Transgenic Alzheimer Rats

Abstract

PURPOSE: This study examined the effects of long-term treadmill exercise training on the anxious-depressive-like behavioral phenotype of transgenic Alzheimer rats in the early stage of Alzheimer's disease (AD) development and provided evidence that exercise alleviated fear-avoidance behavior deficits. METHODS: 2-month-old Male TgF344-AD and wild-type (WT) rats were separated into WT (n = 9), AD (n = 8), and AD + treadmill exercise (Exe) groups (n = 12). Following 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 measure anxious-depressive-like behavior of AD rats. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) analysis, and related assay kits were used to measure levels of inflammatory cytokines, oxidative stress, amyloid-beta production, and tau hyperphosphorylation. RESULTS: Behavioral tests indicated that AD rats aged 12-months did not exhibit spatial learning and memory deficits, but did display anxious-depressive-like behaviors (open field, Center time: P = 0.008; Center entries: P = 0.009; Line crossings: P = 0.001). Long-term exercise significantly prevented anxious-depressive-like behaviors in AD rats (Center time: P = 0.016; Center entries: P = 0.004; Line crossings: P = 0.033). In addition, AD animals displayed enhanced Aβ deposition (P < 0.001), Tau hyperphosphorylation (P < 0.001), microglial activation (P <0.001), inflammatory cytokine release (P < 0.05), and oxidative damage (P < 0.05) that was attenuated significantly after long-term exercise training ( P < 0.05). CONCLUSIONS: Long-term exercise training ameliorated anxious-depressive-like behaviors and improved fear-avoidance behavior in transgenic AD rats, supporting exercise training as an effective strategy to prevent or reduce anxiety, depression and fear-avoidance behavior deficits in the early stages of AD pathogenesis.