Spermidine Down-regulates Pyropsy In Hippocampal Cells To Improve Depression-like Behavior Caused By Sleep Deprivation

[Objective]To investigate whether spermidine can improve depression-like behavior induced by sleep deprivation by down-regulating pyropsy of hippocampal cells.[Methods]Male Sprague-Dawley(SD)rats were adaptively fed for 1 week and randomly divided into 5 groups of 10 rats each : Control group,the highdose Spd monotherapy group(N-SD +10mg/kg Spd),the SD model group(SD+ 0.9%Na Cl),the low-dose Spd protection group(SD+5 mg/kg Spd),and the high-dose Spd protection group(SD+10mg/kg Spd).In this study,the Modified multiple platform method(MMPM)was used to establish a sleep deprivation(SD)rat model for 72 hours of continuous sleep deprivation.The model of sleep deprivation depression disorder was established by behavioral test of forced swimming and tail suspension test.Then,after 21 days of gavage feeding,the rats were again subjected to forced swimming experiment and tail suspension experiment to evaluate depression-like behavior.The rats were anesthetized with 10% chloral hydrate and sacrificed.The hippocampal tissues of the rats were cut off on ice.Western blot was used to detect the expression of NLRP1,NLRP3,Caspase-1,GSDMD,IL-1 and IL-18,the key proteins of pyroptosis.Statistical analysis was performed using Spss22.0 software.[Results] 1.Changes in body weight of experimental rats after sleep deprivation At 0h,the SD group was compared with the Control group(P>0.05).After 72 h,the weight of rats in the SD group was significantly lower than that in the Control group(P<0.001).2.Sleep deprivation can produce depression-like behaviors in experimental rats In the forced swimming experiment,compared with the Control group,the immobility time of rats in the SD group was prolonged(P<0.001),climbing time was shortened(P<0.001),and swimming time was shortened(P<0.001).In the tail suspension experiment,compared with the Control group,the immobility time of rats in the SD group was significantly prolonged(P<0.001).3.Spermidine improves depression-like behavior in sleep-deprived rats In the forced swimming experiment,compared with the SD group,Spd(5mg/kg/d and 10 mg/kg/d)could shorten the immobility time of SD rats(P<0.001),prolong the climbing time of SD rats(P<0.001)and prolong the swimming time of SD rats(P<0.001).In the tail suspension experiment,Spd(5mg/kg/d and 10 mg /kg/d)can significantly reduce the immobility time of SD rats(P<0.001).4.Spermidine down-regulates NLRP1,NLRP3,caspase-1,GSDMD,il-1 and il-18 proteins in the hippocampus of rats Compared with the Control group,SD significantly increased the expression of NLRP1,NLRP3,caspase-1,GSDMD,il-1 and il-18 proteins in the hippocampus of the rats(P<0.05),while Spd(5mg/kg/d and 10mg/kg/d)significantly reduced the expression of NLRP1,NLRP3,caspase-1,GSDMD,il-1 and il-18 proteins induced by SD(P<0.05)in the SD group and the Control group,while no effect was observed in the high-dose Spd monotherapy group(P >0.05).[Conclusion]Spermidine can improve the depression-like behavior of rats induced by sleep deprivation,and its mechanism may be by down-regulating the pyroptosis pathway.