Impacts of chronic sleep deprivation on learning and memory, autophagy and neuronal apoptosis in mice / 中华神经科杂志

ABSTRACT

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.