Treadmill exercise ameliorates chronic REM sleep deprivation-induced anxiety-like behavior and cognitive impairment in C57BL/6J mice

Various sleep disorders have deleterious effects on mental and cognitive performance. Exercise, as an alternative therapeutic strategy, exerts beneficial impacts on human health. In the present study, we aimed to evaluate the effects of 4 weeks treadmill exercise (4W-TE) on anxiety-like behavior and cognitive performance in mice exposed to 2 months REM sleep deprivation (2M-SD) (20 h per day). Behavioral performance of mice in elevated plus maze test (EPM), open field test (OFT), Y maze test (YM) and Morris water maze test (MWM) was recorded and analyzed 28 h after the last day of sleep deprivation. After behavioral tests, various neurotransmitters including norepinephrine (NE), dopamine (DA), serotonin (5-HT) and γ-aminobutyric acid (GABA) in mouse hippocampus were quantified using high performance liquid chromatography. The hippocampal levels of insulin-like growth factor-1 (IGF-1) and brain derived neurotrophic factor (BDNF) were further detected using ELISA. Behavioral data indicated that 2M-SD exposure induced anxiety-like behaviors and cognitive impairment, as evidenced by the decreased open-arm entries in EPM, reduced central area travels in OFT, declined spontaneous alteration in YM and prolonged escaping latency in MWM. In addition, 2M-SD exposure increased NE and DA, decreased 5-HT and GABA, and reduced IGF-1 and BDNF levels in mouse hippocampus. Interestingly, all these behavioral, neurochemical and neurobiological changes can be ameliorated by 4W-TE training. In summary, these findings confirm the beneficial impacts of exercise on health and provide further experimental evidence for future application of exercise as an alternative therapy against the mental and cognitive problems in patients with sleep disorders.