Impacts of chronic sleep deprivation on learning and memory, autophagy and neuronal apoptosis in mice

Objective: To establish chronic sleep deprivation mouse model, evaluate the learning and memory ability of mice and observe autophagy and apoptosis levels in mouse brain. Methods: C57BL/6 mice (n=20) were randomly separated into sleep deprivation group and control group. After 2-month sleep deprivation by using an adapted multiple platform method, the behavioral performance of mice was measured by IntelliCage system. The expression of microtubule associated protein 1 light chain 3-II (LC3-II) and Beclin-1 was detected by Western blotting. Confocol microscopy was used to observe autophagosome. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis level in mouse brain. Results: The results of behavioral test showed that the incorrect visit ratio was much higher in sleep deprivation group than that in control group. Moreover, the expression of LC3-Ⅱ(sleep deprivation group 1.681±0.186, control group 1.125±0.048, t=2.892, P=0.027 6) and Beclin-1(sleep deprivation group 1.144±0.048, control group 1.006±0.017, t=2.721, P=0.018 6) in mouse hippocampus and cortex was significantly elevated in sleep deprivation group than those in control group. Accordingly, the confocal microscopy observation also revealed an increased nuclear LC3-positive puncta in hippocampus and cortex of sleep deprived mice (hippocampus in sleep deprivation group 1.665±0.153, in control group 0.819±0.072, t=5.024, P=0.002 4; cortex in sleep deprivation group 1.925±0.175, in control group 1.195±0.111, t=3.521, P=0.012 5). In addition, TUNEL staining showed a much higher percentage of TUNEL-positive nuclei in these brain regions (hippocampus in sleep deprivation group 47.24±4.15, in control group 19.26±3.72, t=5.025, P=0.007 4; cortex in sleep deprivation group 42.25±1.25, in control group 27.50±3.23, t=4.262, P=0.005 3). Conclusions: Chronic sleep deprivation can impair the learning and memory, increase the expression of LC3-II and Beclin-1, elevate the formation of autophagosome, and promote apoptosis in mouse brain. These findings suggest that autophagy and apoptosis might be involved in the cognitive impairment induced by chronic sleep deprivation.