The Role And Mechanism Of Autophagy In β-amyloid Protein Deposition In Hippocampus Of Chronic Sleep Deprived Mice

Objective: To explore the effect of chronic sleep deprivation on learning and memory function of mice and the role and mechanism of autophagy in the process of hippocampal a β deposition in mice with chronic sleep deprivation.Methods: Forty C57 female mice were randomly divided into control group and experimental group.The experimental group was divided into chronic sleep deprivation group(CSD group),chronic sleep deprivation + rapamycin group(CSD +Rapa group),chronic sleep deprivation + 3-methyladenine group(CSD + 3-m A group)and 10 mice in each group.The experimental group was deprived of sleep for 20 hours every day by MMPM CSD + Rapa group before the end of deprivation In CSD+ 3-m A group,rapamycin(1mg / kg)and 3-m A(2mg / kg)were given intraperitoneally,while in control group and SD group,the same amount of saline was given intraperitoneally for 12 consecutive days;the general situation of the four groups of mice was observed,and Morris water maze system was used to test the behavioral changes of the four groups of mice after experimental intervention;after extracting the hippocampal tissue of mice,he staining was used to observe the morphology of the hippocampal tissue of the four groups of mice The expression of aβ 42,LC3,mTOR and PI3 K in hippocampus of four groups of mice was detected by IHC,and the expression of LC3,mTOR and PI3 K in hippocampus of four groups of mice was detected by WB.Results: 1.General situation of mice: there was no significant change in the control group,the spirit of mice in CSD group and CSD + 3-m A group was depressed,appetite was decreased,the glossiness of hair was decreased,and the mice in CSD +Rapa group were easily provoked,the mental state and weight of mice in CSD + rapa group were significantly changed.2.Behavioral changes: compared with the control group,the escape latency was significantly longer in CSD Group [(31.17 ± 8.63)vs(19.15 ± 4.5),P < 0.05],CSD + Rapa Group [(25.87 ± 9.05)vs(19.15 ± 4.5),P <0.05],CSD + 3m A Group [(32.55 ± 9.39)vs(19.15 ± 4.5),[(14.52 ± 2.94)vs(33.8 ±8.97),P < 0.05].Compared with CSD + 3-m A group,the target quadrant dwell time of CSD + Rapa group was longer [(21.25 ± 6.41)vs(14.52 ± 2.94),P < 0.05].3.Morphological changes of hippocampal cells in mice: the control group had complete morphology,clear boundary,close arrangement and no obvious damage in cell structure;the CSD group had loose arrangement,wider intercellular space,shrinking nucleus,smaller cell body and fewer cells;the CSD + Rapa group had decreased number of nerve cells and light degree of nucleolar shrinkage;the CSD + 3-m A group had arranged neurons Looseness,decrease of cell number were more serious than the other three groups,and the injury was more serious.4.Changes of a β 42 positive reactants in the hippocampus of mice: compared with the control group,the a β 42 positive reactants in the other three groups increased significantly.5.WB was used to detect the expression of LC3,PI3 K and mTOR in the hippocampus of mice: compared with the control group,LC3-II / lc3-i in the CSD group and CSD + Rapa group increased,P < 0.05;the increase in the CSD + 3-m A group was unidentified,P > 0.05;compared with the control group,the expression of mTOR in the CSD group and CSD+ 3-m A group increased,P < 0.05;the expression of mTOR in the CSD + Rapa group decreased,P < 0.05;compared with the CSD + Rapa group,the expression of mTOR in the CSD + Rapa group decreased,Compared with CSD group,P < 0.05,the expression level of mTOR in CSD + 3-m A group was higher(P < 0.05);compared with the control group,the expression level of PI3 K in CSD group and CSD + Rapa group was higher(P < 0.05),and the increase in CSD + 3-m A group was unidentified(P > 0.05).Compared with CSD group,the expression level of PI3 K in CSD + 3-m A group decreased(P < 0.05).Conclusion:1.Chronic sleep deprivation can lead to morphological changes of hippocampal neurons,promote the aggregation of Aβ 42 in the hippocampus of mice,and reduce the cognitive function of mice.2.Chronic sleep deprivation can regulate autophagy activity through PI3 K / Akt /mTOR signaling pathway,and promote autophagy activity of mouse hippocampal neurons,which may be the factor affecting the pathogenesis and development of Alzheimer’s disease.