Altered ADAR1 And 5-HT2CR In The Social Isolation Stress-induced Cognitive Deficits Mice

Background and objectiveStress plays an important role in the human life.It has been reported that all human diseases mechanisms are related to the activation of stress.Stress is defined as the non-specific reaction of body in response to adapting to the various internal and external environmental factors including social and psychological factors.Stress is a common phenomenon for all living beings,which is a kind of biological instinct.Stressors and human health are closely related.Psychosocial stress is an important way of damaging the human health.The relationship between stress and disease has been a hot topic.Social isolation regarded as a chronic stressor,refers to the lack of relationship with the social contact completely or partly belonging to social stress.We used social isolation stress model to research altered ADAR1 and 5-HT2CR in the social isolation stress-induced cognitive deficits mice.The change of cognitive function was measured by behavioral tests,change of the expression of 5-HT2C receptor and ADAR1 in the brain were measured by biochemistry and molecular biology techniques.Exploring the mechanisms of social isolation induced cognitive dysfunction will provide the basis of revealing the related mechanism and be beneficial for early diagnosis and prevention strategies in social isolation induced mental disorders.MethodsThe healthy Kunming mice were isolated for 2,4 and 8 weeks individually since postnatal 21 days respectively to set up isolation mice model.The behavioral tests were used to measure the change of cognitive ability.We also arranged re-socialization group.The same age mice without isolation were regarded as control groups.Immunohistochemistry and western blot were used to evaluate the alterations of ADAR1 and 5-HT2CR in the social isolation-induced cognitive deficits mice.Results1.In the Object recognition test(ORT),the discrimination index(DI)of the mice undergoing 2,4 and 8 weeks of social isolation(SI)decreased significantly as compared to that of the same age mice without isolation.No obvious difference was found between re-socialization group(SI 2WR)and the same age mice without isolation(C 4W);2.In the Object location test(OLT),the DI of the mice undergoing 2,4 and 8 weeks of SI decreased significantly as compared to that of the same age mice without isolation.No obvious difference was found between SI 2WR and the same age mice without isolation(C 4W);3.In spontaneous alternation test,alternation times of SI 2W group were less than those of C 2W group in day 1 and day 4;in day 2,alternation times of SI 4W were more than those of C 4W group;in day 4,alternation times of SI 8W were more than those of C 8W group.The alternation times of SI 2WR showed no obvious changes as compared with those of the same age mice without isolation stress;4.Immunohistochemistry of brain results of ADAR1 showed that as compared to the mice without isolation in the same age,the immunoreactivity of ADAR1 enhanced significantly in hippocampus and frontal cortex in the mice undergoing 2,4 and 8 weeks social isolation stress;The number of ADAR1 immunoreactive positive cells in frontal cortex of 2,4 and 8 weeks isolation mice increased as compared with the same age mice without isolation;In CA1 and hilus,the number of ADAR1 immunoreactive positive cells increased obviously in 2.4 and 8 weeks isolation mice;the optical density of ADAR1 in frontal cortex,CAl and hilus were stronger significantly in the mice of 2 weeks social isolation rearing;The re-socialization group reduced obviously as compared with that of the mice undergoing isolation.5.In comparison with the same age mice without isolation,the expression of ADAR1 in the hippocampus elevated significantly in 2 weeks isolation rearing mice as well as that in the frontal cortex of 8 weeks isolation rearing mice.Furthermore,the protein expression of 5-HT2CR in the hippocampus of 2 and 8 weeks isolation rearing mice as well as that in the frontal cortex of 4 and 8 weeks isolation rearing mice enhanced obviously as compared to those in the same age mice without isolation.Conclusions1.Different degree social isolation stresses lead to spatial and non-spatial disability in the mice;2.Different degree social isolation stresses lead to abnormal working memory in the mice;3.Different degree social isolation stresses lead to the abnormal expression of ADAR1 and 5-HT2CR in the hippocampus and frontal cortex;4.Re-socialization can recover the abnormal cognitive function and abnormal expression of ADAR1 and 5-HT2CR.