Study On Peripheral Blood Adenosine Levels And Related Immune Function In Patients With Insomnia

Background Insomnia is a common sleep disorder that causes immune dysfunction and cognitive impairment.Adenosine is widely distributed in the brain and periphery of the human body.It plays a role in promoting sleep by regulating nerve cell function and the release of neurotransmitters.Adenosine signal includes adenosine key enzyme and adenosine receptors,which also related to sleep regulation.Studies have shown that sleep disturbance induces abnormal expression of immune inflammatory factors,and some inflammatory factors also have sleep promoting effect in the brain.In astrocytes,adenosine and immuno-inflammatory factors work together to regulate the process of sleep and arousal.Insomnia can cause impairment of cognitive function,especially the reduction of working memory and spatial recognition.Previous studies have focused on the healthy population who suffered from sleep deprivation.There are few studies on peripheral adenosine related indicators and immune function in patients with insomnia,especially those who meet the diagnostic criteria for chronic insomnia,and there is also a lack of research on the association of these indicators with memory functions.Objective In order to explore the changes of peripheral blood adenosine level and immune inflammatory factors in patients with chronic insomnia disorder(CID)and insomnia comorbidity depression(ICD),and whether the changes of indicators are related to the impairment of memory in insomnia patients.Methods A total of 69 patients who complained of insomnia were recruited for the first consultation in the department of sleep and neurology.According to the ICSD-3 diagnostic criteria,there were 37 CID cases(13 males and 24 females)and 32 ICD cases(6 males and 26 females).A control group of 47 patients(13 males and 34 females)were originated from the physical examination center.We collected patient basic data such as age,gender and educational level.The Pittsburgh Sleep Quality Index(PSQI)was used to assess the quality of sleep by professional physicians.The Hamilton Depression Inventory Scale 17(HAMD-17)evaluated the patient's depression and the Montreal Cognitive Scale(MoCA)assessed overall cognitive function.The patients were instructed to complete nine boxes of labyrinth experiment and evaluated the relevant memory capacities.The venous blood was taken from the subjects,one part was used to separate lymphocytes,the other part was used to centrifuge the plasma and put it in-80 ? refrigerator.The level of plasma adenosine was detected by high performance liquid chromatography mass spectrometry.The ADA level was detected by enzyme-linked immunosorbent assay(ELISA).The lymphocyte transformation rate was measured by PHA-stimulated lymphocyte transformation assay.Luminex liquid-phase chip technique was used to detect peripheral blood IL-1?,TNF-?,and IL-4 levels.Results The basic data of CID group,ICD group and control group including age,gender and educational level were not statistical different.The PSQI scores of CID group and ICD group were higher than that of control group(P<0.05),but there was no statistical different between the two groups.HMAD-17 scores in the CID group and ICD group were higher than that in the normal control group(P<0.05),and the score in the ICD group was significantly higher than that in the CID group(P<0.05).Object and spatial reference memory,object and spatial working memory,object recognition memory scores were statistical different between the three groups(P<0.05),and the numbers of error in object work,space work,and object recognition memory in CID group were higher than those in the control group(P<0.05).The numbers of all types of memory error in ICD group were higher than those in the control group(P<0.05).The adenosine levels in the three groups were statistically different(P<0.05),and the adenosine levels in the CID group and the ICD group were lower than that in the control group(P<0.05).There was a statistically significant difference between the three groups in the ADA levels(P<0.05).The ADA level in the ICD group was higher than that in the control group(P<0.05).The ADA levels between the CID and the control groups were no significant defferent.The lymphocyte transformation rates were statistically significant difference between three groups(P<0.05).The lymphocyte transformation rate of ICD group was higher than that of control group(P<0.05).There was no statistical difference between ICD and CID groups.There was a statistically significant difference between the three groups of TNF-a(P<0.05).The levels of TNF-a in the ICD group and the ICD group were higher than that in the control group(P<0.05),and the level of TNF-a in the CID group was lower than that in the ICD group(P<0.05).IL-1? levels in CID group and ICD group were higher than that in control group(P<0.05),and IL-1? level in ICD group was higher than that in CID group(P<0.05).IL-4 levels in the three groups were no statistical difference.The IL-4 level in the CID group was higher than that in the control group(P<0.05).Conclusion Patients with insomnia(CID and ICD)had lower adenosine level in the peripheral blood,which affects the ability to promote sleep and inhibit wakefulness.The lymphocyte transformation rate and ADA level were increased in ICD group.Patients with insomnia had higher TNF-a and IL-1? levels,which can promote sleep.CID group had higher IL-4 level that negative control of TNF-? and IL-1?.It suggests that insomnia affects the immune function,and the body will adjust the changes of the immune state changes caused by insomnia.Due to the immunosuppressive effect of adenosine,the decrease of peripheral blood adenosine level is accompanied by up-regulation of the expression of immune cytokines,but the pathway and mechanism are deserved further exploration.In addition,the degree of memory impairment in patients with insomnia is associated with changes in TNF-?,IL-1? and adenosine levels.Memory impairment may be due to their effects.