Effects Of General Anesthesia On Neurotransmitters,Aβ And Tau Proteins In Cerebrospinal Fluid Of Rats After Sleep Deprivation

OBJECTIVE: To investigate the effects of propofol,dexmedetomidine and ketamine on neurotransmitters,β-amyloid peptide(Aβ)and Tau protein in the cerebrospinal fluid of rats after sleep deprivation and their mechanisms,and to provide guidance for the anesthesia or treatment of insomnia patients in clinical practice.METHODS: Forty male SPF Sprague-Dawley(SD)rats aged 3-4 months were randomly divided into 5 groups:They were deprived of Sleep deprivation(SD),Propofol after Sleep deprivation(PSD),Dex after Sleep deprivation(DSD),Ketamine after Sleep deprivation(Ketamine)and platform control group(Sleep Nature,SN).All patients were deprived of sleep by a modified multi-platform sleep deprivation model(MMPM).The sleep deprivation of SD,PSD,DSD and KSD groups began at 7:00 for72 h.After sleep deprivation,the PSD,DSD and KSD groups were given propofol(100mg/Kg),dexmedetomidine(100mg/Kg)and ketamine(80mg/Kg),respectively,to maintain anesthesia for 3h.The SN group entered the large platform for free activity for 72 h.Cerebrospinal fluid(CSF)was collected after intraperitoneal injection of 0.35 m L 10% chloral hydrate.The contents of dopamine(DA),5-hyrdoxytryptamine(5-HT),norepinephrine(NE),acetylcholine(Ach),glutamate(Glu),γ-aminobutyric acid(GABA)neurotransmitters,Aβ and Tau proteins in CSF were measured by enzymatic linked immunosorbent assay(ELISA).The analysis software was SPSS23.0(SPSS Inc.,Chicago,USA).One-way ANOVA was used to analyze the relationship between each neurotransmitter and the content of Aβ and Tau protein.Two-sided test was used for statistical analysis,and the significance test level was set at α=0.05.Results:1.Changes in the body weight of rats: After sleep deprivation,the weight of SD,PSD,DSD and KSD groups decreased compared with that before sleep deprivation,and the difference was statistically significant(P<0.05).2.Concentration of neurotransmitters in cerebrospinal fluid(CSF): One-way ANOVA was conducted among the five groups,and the results showed statistically significant differences among the groups(P < 0.05).2.1 DA: Through pair comparison and further analysis of differences between groups,it was found that DA concentration in the DSD group and the KSD group was higher than that in the other three groups(P < 0.05).DA concentration in the SD group was lower than that in the DSD group and the KSD group,and higher than that in the SN group and the PSD group(P < 0.05).There was no significant difference between the DSD group and the KSD group,and between the SN group and the PSD group(P > 0.05).2.2 NE: The NE concentration in KSD group was higher than that in SD group and SN group(P < 0.05),and the NE concentration in PSD group and DSD group was lower than that in SN group(P < 0.05).There was no statistical significance between PSD group and DSD(P > 0.05).2.3 5-HT: The concentration of 5-HT in DSD group was higher than that in SD group and SN group(P < 0.05),and the concentration of 5-HT in KSD group and PSD group was lower than that in SN group(P < 0.05).There was no statistical significance between PSD group and KSD group(P > 0.05).2.4 Ach and Glu: The concentrations of Ach and Glu in SD group were higher than those in SN group(P < 0.05),and the concentrations of Ach in PSD group,DSD group and KSD group were lower than those in SN group(P < 0.05).There was no statistical significance between PSD group,DSD group and KSD(P > 0.05).2.5 GABA: The concentration of GABA in PSD group,DSD group and KSD group was higher than that in SN group(P < 0.05),and the concentration of GABA in SN group was higher than that in SD group(P < 0.05).There was no statistical significance between PSD group,DSD group and KSD group(P > 0.05).3.The contents of Aβ and Tau protein in cerebrospinal fluid in KSD and PSD groups were higher than those in SD group(P < 0.05),SD group was higher than that in DSD group,and KSD group was higher than that in SN group(P < 0.05).There was no statistical significance between KSD and PSD groups(P > 0.05).Conclusion:1.Sleep deprivation increases the concentration of excitatory neurotransmitters(DA,NE,5-HT,Ach,Glu)and decreases the concentration of inhibitory neurotransmitters(GABA)in cerebrospinal fluid,and long-term sleep deprivation will cause physical fatigue,emotional apathy and other negative effects.2.Propofol decreased the concentration of five excitatory neurotransmitters in cerebrospinal fluid,and increased the influence of inhibitory neurotransmitters,which may aggravate the negative emotions after sleep deprivation;3.Ketamine increases the concentrations of DA and NE in cerebrospinal fluid after sleep deprivation,which may be involved in the anti-depressive mechanism.4.Dexmedetomidine may relieve the adverse mood caused by sleep deprivation through its influence on DA and 5-HT in cerebrospinal fluid after sleep deprivation,and may be related to the easy arousal characteristic of Dexmedetomidine;5.The levels of nociceptive proteins(Aβ and Tau)in CSF were decreased in the dexmedetomidine group,while the levels were increased by sleep deprivation,propofol and ketamine6.Compared with propofol and ketamine,dexmedetomidine has better effects on sleep and emotion regulation,and can reverse the increase of harmful proteins caused by sleep deprivation,so it should be more widely used in clinical practice.