Effects Of Sleep Deprivation On Learning And Memory And Brain Aβ-related Metabolism In Rats

Objectives: In this study,the modified multiple platform method(MMPM)was used to create a sleep deprivation(SD)model.We observe the effect of SD on learning and memory and Aβ metabolism in rats to explore the possible mechanisms.Methods: Three-month-old Specific Pathogen Free(SPF)Sprague-Dawley rats were randomly divided into 5 groups: two SD groups(i.e.SD-2d and SD-4d),two platform control(PC)groups(i.e.PC-2d and PC-4d)and a home cage control group(CC).For the two SD groups,the MMPM was used to induce SD.The Morris water maze was used to test spatial learning and memory in the rats from all five groups.Another group of rats wasanesthetized and killed immediately after SD,and the corresponding brain tissues and blood samples were harvested according to the experimental design.The levels of plasma corticosterone and Aβ1-42 and Aβ1-40 in the cerebral cortex were detected by ELISA.Real-time fluorescence quantitative RT-PCR was used to determine the gene transcription level of ADAM10,BACE1,NEP,and IDE in the brain.Western blotting was used to determine the protein expression levels of APP,s APPβ,ADAM10 and BACE1.Results:1.Compared with the PC groups,the SD groups exhibited a significantly increased escape latency in the Morris water maze test.After the platform was removed,the time spent in the target quadrant and the average number of times the animals crossed the platform location were significantly lower in the SD groups than inthe PC groups,whereas there was no significant difference between the PC groups and the CC group.2.After SD,the levels of Aβ1-42 and Aβ1-40 and the ratio of Aβ1-42/Aβ1-40 were significantly elevated in both the SD-2d rats and the SD-4d rats compared to the levels in the PC-2d group and the PC-4d group.3.The plasma corticosterone levels did not differ among the five groups.4.Theprotein expression levels of APP did not significantly differ in the 5 groups compared with those in the PC groups(P>0.05).The expression of ADAM10 was increased in the SD-2d rats(P<0.001).The level of ADAM10 in the SD-4d rats was significantly decreased compared with that in the SD-2d rats and did not differ from that in the controls.Compared to the PC-2d group,the SD-2d rats displayed a 1.6-fold increase in the levels of BACE1(P<0.001)and a 1.9-fold increase in the levels of s APPβ(P<0.001),asdeterminedby Western blotting.This trend was more obvious in the SD-4d rats,with a 1.9-fold increase in the levels of BACE1(P<0.001)and a 2.4-fold increase in the levels of s APPβ(P<0.001).5.The RT-PCR results indicated that the gene expression levels of NEP and IDE in the brain did not significantly differ among the 5 groups after SD(P>0.05).In addition,the gene expression levels of ADAM10 and BACE1 in the brain were consistent with the Western blotting results.Conclusions:Our data demonstrated that acute SD could have adverse effects on learning and memory.In addition,SD can increase the peptide levels of Aβ1-42 and Aβ1-40 by elevating the levels of BACE1.Acute SD causedan imbalance of Aβmetabolism throughincreased production of Aβ,whereas no significant alterations in Aβdegradation were observed.