The Effect Of ADAR1 In Social Isolation Stress-induced Abnormal Behavior Of BALB/c Mice

Objective The social isolation stress model of BALB/c mice was established to study the change of behavior induced by social isolation stress.The ADAR1(adenosine deaminase acting on RNA 1)inhibitor and inducer were treated to discuss the effect of ADAR1 inhibitor and inducer on the abnormal behavior of BALB/c mice induced by social isolation stress.Methods The healthy male BALB/c mice of 21 days were reared in a single cage for 4 weeks and established the social isolation stress model.The same age healthy male BALB/c mice were reared by group-housed as control group.The mice were randomly divided into isolation group,group-housed control group,drug treatment group(ADAR1 inhibitor isolation group and ADAR1 inducer isolation group),and drug treatment control group(ADAR1 inhibitor group-housed group and ADAR1 inducer group-housed group).The drug treatment group and drug treatment control group were treated with ADAR1 inhibitor EHNA or ADAR1 inducer IFN-y.The isolation group and group-housed control group were treated with physiological saline as drug treatment control.The open field test,new object recognition test.Resident-Intruder test,tail suspension test,and forced swimming test were used to detect the change of autonomous behavior,exploratory behavior,cognitive function,aggressive behavior,and the desperate degree of BALB/c mice.Then using immunohistochemistry and western blot to detect the change of ADAR1 and 5-HT2cR(5-HT2C receptor)immunoreactivity or expressionResults Behavioral results show that:1.In the open field test,compared with the group-housed control group,the total distance and the time spent in central area of the isolation group mice reduced significantly.Compared with the isolation group,the total distance and the time spent in central area of the ADAR1 inducer isolation group mice increased significantly.2.In the new object recognition test,compared with the group-housed control group,the discrimination index of the isolation group mice decreased significantly.The discrimination index of ADAR1 inducer isolation group mice increased significantly While the discrimination index of ADAR1 inhibitor isolation group decreased significantly than that of the isolation group3.In Resident-Intruder test,compared with the group-housed control group,the latency of first bite in isolation group mice shortened significantly,but the times of attack increased obviously,and the duration of biting genital and sides also increased.Compared with the isolation group,the latency of first bite in ADAR1 inducer isolation group mice prolonged significantly,but the times of attack reduced significantly,and the duration of biting genital and sides also reduced significantly.compared with the isolation group,the the latency of first bite in inhibitor isolation group mice shortened significantly,and the duration of biting sides increased obviously.4.In the tail suspension test and forced swimming test,the immobility time of the isolated group mice increased significantly compared with the group-housed control group,and the immobility time of the ADAR1 inducer isolation group mice decreased significantly compared with the isolation group.The results of immunohistochemistry showed that the optical density of ADAR1 positive neurons in prefrontal cortex,hippocampus,and amygdala of isolation group mice decreased significantly than that of group-housed control group.Compared with the isolation group1 the optical density of ADAR1 positive neurons in the prefrontal cortex,hippocampus,and amygdala of the ADAR1 inducer isolation group mice increased significantly,but there was no significant difference in the ADAR1 inhibitor isolation group The results of western blot showed that the expression of ADAR1 and 5-HT2cR in prefrontal cortex,hippocampus,and amygdala of isolation group mice were decreased significantly than those of group-housed control group.Compared with the isolation group,the expression of ADAR1 and 5-HT2cR in prefrontal cortex,hippocampus,and amygdala of the ADAR1 inducer isolation group mice increased significantly.Conclusions 1.After 4 weeks social isolation stress,the BALB/c mice developed depressive behavior,the degree of despair increased?and its non spatial cognitive function weakened,meanwhile,the aggressive behavior enhanced obviously2.The expression of ADAR1 and 5-HT2CR in prefrontal cortex,hippocampus,and amygdala of BALB/c mice were decreased after 4 weeks social isolation stress.3.ADAR1 inhibitor EHNA aggravated the non spatial cognitive function impairment and the enhanced aggressive behavior induced by social isolation stress in BALB/c mice.4.ADAR1 inducer IFN-? alleviated abnormal behavior induced by social isolation stress in BALB/c mice.5.ADAR1 inducer IFN-y partially reverted the low expression of ADAR1 and 5-HT2CR in prefrontal cortex,hippocampus,and amygdala in BALB/c mice by social isolation stress.