Changed Serum Levels Of Neurotensin,Pannexin1 And Sestrin2 And Their Correlations With Sleep Quality And Cognitive Function In The Patients With Chronic Insomnia

BackgroundThe occurrence and development of insomnia is the result of multiple factors,including neurotransmitter disorders,neurodevelopment and function,inflammatory cytokines,and cortisol dynamics.With the development of imageology,brain injury in insomnia patients has been gradually verified.As the most basic structural and functional unit of the brain nervous system,neurons are rarely studied on the microscopic brain structures(neurons,glial cells,etc.)in insomnia patients.And a few studies have also focused on animal models.Exploring the changes of neuronal function and the relationship between sleep quality and cognitive function in insomnia patients will help to further understand the mechanisms of insomnia.ObjectivesTo investigate changes in serum concentrations of Neurotensin(NTs),Pannexin1(PANX1),and Sestrin2(SESN2)in patients with chronic insomnia disorder(CID),and whether serum levels of these three biomarkers correlate with sleep quality and cognitive function.MethodsA total of 65 patients with CID from the Sleep Disorders Clinic and 56 good sleepers(HC)as controls were recruited.General data including sex,age,years of education,body mass index(BMI),personal history,disease history,life history,and family genetic history were collected.The Pittsburgh Sleep Quality Index(PSQI)and Polysomnography(PSG)were used to assess subjective and objective sleep quality.The Hamilton Depression Rating Scale-17(HAMD-17)was used to evaluate depression level.The Chinese-Beijing Version of Montreal Cognitive Assessment(Mo CA-C)was used to assess the overall cognitive function of subjects.The Nine Box Maze Test(NBMT)was used to assess Objective memory function.The Blue Velvet Arena Test(BVAT)was used to detect spatial memory function of subjects.Neurotensin,Pannexin1 and Sestrin2 serum levels were measured by enzyme-linked immunosorbent assay.Results1.General information:There were no significant differences in gender ratio(x ~2=1.358,P=0.244),age(Z=-1.834,P=0.067),years of education(Z=-1.307,P=0.191)and BMI(Z=-0.993,P=0.321)between the two groups.The HAMD-17score in CID group was significantly higher than that in HC group(Z=-8.989,P=0.000).2.Sleep quality:PSQI score in CID group was significantly higher than that in HC group(Z=-9.562,P=0.000).PSG results showed that:In CID group,total sleep time,long wake-time after sleep onset,low sleep efficiency,long sleep onset latency,long wake time,short N3 sleep duration in Non-Rapid Eye Moment(NREM)sleep and a small percentage of N3 sleep time in total sleep time.3.Cognitive function:Mo CA-C score in CID group was significantly decreased(Z=-4.380,P=0.000).In the NBMT,object working memory(Z=-5.530,P=0.000)and spatial working memory(Z=-2.268,P=0.023)erroneous numbers in patients with CID were significantly higher than those in the HC group.In the BVAT,the mean erroneous distance of CID group was significantly longer than that of HC group(Z=-4.424,P=0.000).4.Serum marker levels:In CID group,the NTs(t=5.210,P=0.000)and the PANX1(Z=-4.169,P=0.000)levels were higher than those in HC group,and the SESN2(Z=-2.438,P=0.015)level was lower than those in HC group.5.Correlation between serum marker levels with sleep quality in CID group:Spearman correlation analysis showed that there is no correlation between serum marker levels and PSQI score.PANX1 was positively correlated with total sleep time(r=0.562,P=0.002),negatively correlated with wake-time after sleep onset(r=-0.590,P=0.001),positively correlated with sleep efficiency(r=0.588,P=0.001),and negatively correlated with wakefulness duration(r=-0.582,P=0.001).SESN2 was positively correlated with the percentage of rapid eye moment(r=0.442,P=0.016),and negatively correlated with the percentage of N2 sleep time in total sleep time(r=-0.394,P=0.034).6.Correlation between serum marker levels with depression degree and cognitive parameters in CID group:Spearman correlation analysis showed that there was no significant correlation between serum marker levels with HAMD score,Mo CA-C score and the numbers of memory error in NBMT.NTs was positively correlated with the mean erroneous distance of BVAT(r=0.263,P=0.035),and PANX1 was significantly positively correlated with the mean erroneous distance of BVAT(r=0.328,P=0.008).7.Receiver Operating Characteristic(ROC)curves of NTs,PANX1 and SESN2were plotted to diagnose CID.The results showed that NTs and PANX1 could distinguish CID and healthy subjects with high sensitivity.ConclusionAbnormal serum levels of NTs,PANX1,and SESN2 in patients with CID indicate impaired neuronal function,which may be associated with poor sleep quality and/or cognitive dysfunction.