Experimental Study Of Moderate Intensity Swimming Exercise Affecting The Cerebral HINT1 Expression In The Depression Mice Induced By CUMS

Objectives : Depression is a chronic,highly recurrent psychiatric disease.Research has found that exercise can play an anti-depressant role,although there are many mechanisms associated with it.However,there are few mechanisms involved in brain changes,and histidine triad nucleotide-binding protein 1(HINT1)has a wide range of expression in the brain region,and plays a significant role in depression and other psychiatric disorders.Therefore,it is suggested that exercise and the expression of HINT1 in the brain are closely related to the improvement of depressive symptoms.We used chronic unpredictable mild stress chronic unpredictable mild stress(CUMS)to induce depression-like behavior in mice.Through research,We can further investigate whether the expression of HINT1 in the brain is a possible mechanism for exercise to alleviate depressive symptoms.And to explore the mechanism of HINT1 itself,so as to provide relevant scientific basis for future clinical treatment,drug research and development,as well as lay the foundation for the follow-up related experiments.Methods: 1.Thirty-one 5-week-old male C57BL/6 mice were randomly divided into normal group(n=7),swimming CUMS group(n=12)and CUMS group(n=12).The mice of swimming CUMS group and CUMS group were stimulated with CUMS for 7 weeks,In the swimming CUMS group,the moderate intensity swimming intervention was increased by 60 min / d from the 4th week of stimulation,5 days a week for 4 weeks.2.After CUMS stimulation,the mice in each group were tested for behavior.The effects of modeling were evaluated by sugar intake rate,forced swimming rest time,rest time of tail suspension test,erect times of open field experiment and movement time of peripheral area.3.The brain of the experimental mice was continuously frozen from front to back,the thickness of the slices was 40 ?m,and Immunohistochemical staining of diaminobenzidine(DAB)was used.The expression of HINT1 positive cells in the cerebral cortex,hippocampus and striatum of mice was observed under light microscope.4.The hippocampus,striatum,cortex and protein tissue were isolated from the experimental mice.Western blot technique was used to detect the expression of HINT1 protein in these brain regions.Results : 1.In the sugar-water intake rate,the normal group was higher than that of the swimming CUMS(p<0.05)group,and the swimming CUMS group was higher than that of the CUMS group(p<0.01).In the forced swimming rest time,there was no significant difference between the normal group and the swimming CUMS group(p>0.05),but the swimming CUMS group was higher than the CUMS group(p<0.01).In the rest time of tail suspension,there was no significant difference between the normal group and the swimming CUMS group(p>0.05),but the swimming CUMS group was higher than the CUMS group(p<0.05).In the number of erect open fields,there was no significant difference between the normal group and the swimming CUMS group(p>0.05),but the swimming CUMS group was higher than the CUMS group(p<0.05).In the activity time of the area around the open field,there was no significant difference in the activity time between the normal group and the swimming CUMS group(p>0.05),but the swimming CUMS group was higher than the CUMS group(p<0.01).2.In the cerebral cortex of mice,the expression of HINT1 positive cells was significantly higher in the normal group than that in the swimming CUMS group and CUMS group(p<0.01),and that in the swimming CUMS group was higher than that in the CUMS group(p<0.01).The results of immunoblotting showed that the expression of HINT1 in normal cerebral cortex of mice was higher than that of swimming CUMS group and CUMS group(p<0.01),and that of swimming CUMS group was higher than that of CUMS group(p<0.01).3.In the hippocampus of mice,the expression of HINT1 positive cells in each group was significantly different by Immunohistochemical method was significantly higher in the normal group than that in the swimming CUMS group and CUMS group(p<0.01),and that in the swimming CUMS group was higher than that in the CUMS group(p<0.01).The results of immunoblotting showed that the expression of HINT1 in hippocampus of normal mice was higher than that of swimming CUMS group and CUMS group(p<0.05),and that of swimming CUMS group was higher than that of CUMS group(p<0.05).4.In the striatum of mice,By means of immunohistochemistry,it was found that,There was no significant difference in the expression of positive cells between swimming CUMS group and CUMS group(p>0.05).The results of immunoblotting showed that there was no significant difference in the relative expression of hint1 in striatum of each group(p>0.05).Conclusions: 1.According to the related behavioral test,the model of depression induced by CUMS was successfully established in 7 weeks.Moderate intensity swimming can effectively slow down the development trend of depressive symptoms and play a good role in improving depression-like behavior.2.Moderate intensity swimming could increase the expression of HINT1 in the cerebral cortex of depressed mice.It shows good antidepressant effect and has antidepressant mechanism correlation.3.Moderate intensity swimming could increase the expression of HINT1 in hippocampus of depressed mice.It shows good antidepressant effect and has antidepressant mechanism correlation.4.In striatum,exercise and HINT1 may not be associated with antidepressant mechanisms.