Effect Of Running Exercise On Neurogenesis And Glial Differentiation In Hippocampus Of Depression Model Rats

PART ONE THE BEHAVIORAL CHANGES OF THE DEPRESSION MODEL RATS INDUCED BY CHRONIC UNPREDICTED STRESS AND THE EFFECT OF RUNNING EXERCISE ON THE BEHAVIORS OF DEPRESSION MODEL RATSObjective:To investigate the effect of running exercise on the behaviors of depression model rats induced by chronic unpredicted stress in order to further provide the behavioral basis for the next study on the mechanism of the antidepression of running exercise.Methods: In the current study,we used sucrose preference test and open field test to assess the ability of sucrose preference and locomotor activity of the Sprague-Dawley rats in unstressed control group and depressed model group before the latter were adminstered the chronic unpredicted stress.The Sprague-Dawley rats were adminstered 7-week chronic unpredicted stress,sucrose preference test and elevated plus maze test were used to assess the anhedonia and anxious like behavior of these model rats,repectively.Then,the depressed model rats were divided into model control group and running model group,and the latter underwent 6-week running exercise.At last,all the rats in the three groups were adminstered the behavioral tests that included sucrose preference test and elevated plus maze test.Results: Before the chronic unpredicted stress schedule,there was no significant difference in sucrose preference between the unstressed control group and the depressed model group(p>0.05).Similarly,there were no significant differences in the parameters of the open field test including total route in the open field,the time spent in center area of the open field and the mean speed in the open field tast(p>0.05),between the unstressed control group and the depressed model group.The present results showed that 7-week chronic unpredicted stress significantly reduced the sucrose preference in the depressed model group when compared to that in the unstressed control group(p<0.05).In elevated plus maze test,the percentage of the number of the open arm entries and the percentage of the time spending in the open arms was significantly lower in the depressed model group than in the unstressed control group(p<0.05).However,the total number of arm entries on the elevated plus maze test was not significantly different between the unstressed control group and the depressed model group(p>0.05).At the end of the exercise schedule,sucrose preference was significantly greater in the running model group than in the model control group(p<0.05).In elevated plus maze test,the percentage of the number of the open arm entries and the percentage of the time spending in the open arms were significantly increased in the running model group,when compared to those in the model control group(p<0.05).The total number of arm entries on the elevated plus maze test was not significantly different in the three groups(p>0.05).Conclusions: 1.Seven-week chronic unpredicted stress induced depressed like behavior—anhedonia accompanied by anxious like behaviors,which indicated the depressed model used in the study was successfully established.2.Continuous six-week running exercise significantly improved the depressed like behavior,and it also improved the anxious behaviors of the depressed model rats.PART TWO THE CHANGES OF NEURONS AND NEW BORN NEURONS IN HIPPOCAMPUS OF DEPRESSION MODEL RATS AND THE EFFECT OF RUNNING EXERCISE ON THE NEURONS AND NEW BORN NEURONS IN HIPPOCAMPUS OF DEPRESSION MODEL RATSObjective:To investigate the changes of the neurons in different hippocampal subregions and the new born neurons in dentate gyrus of hippocampus in depression model rats induced by chronic unpredicted stress,as well as the effect of running exercise on the neurons in different hippocampal subregions and the new born neurons in dentate gyrus of hippocampus in depression model rats,in order to further explore the celluler mechanism of depression and the antidepression of running exercise.Methods: In the present study,we used behavioral mechods,toluidine blue staining,immunohistochemistry technique and stereological method to investigate the changes of the neurons and the newborn neurons of the hippocampus in depression model rats and the effect of running exercise on the newborn neurons of the hippocampus in depression model rats.The Sprague-Dawley rats were adminstered 7-week chronic unpredicted stress and following 6-week running exercise.At the second week of running exercise schedule,the rats of each group were intraperitoneally injected with 10 mg/ml,100 mg/kg BRDU per day for a week.After the behavioral tests,the toluidine blue staining,immunohistochemistry staining and stereological quantification of the neurons and the newborn neurons of hippocampus in three groups were done,respectively.Results: There were no significant changes in the total neurons of dentate gyrus,CA1 subregion and CA3 subregion in the hippocampus of rats in the three groups(p>0.05).After 7-week chronic unpredicted stress,the total number of the newborn neurons was significantly reduced in dentate gyrus of hippocampus of the depressed model rats,when compared to the unstressed control group(p<0.05).Following the 6 weeks of exercise,the total number of the newborn neurons in the dentate gyrus of the hippocampus of the running model rats was significantly increased when compared to that in both model control group and unstressed control group(p<0.05).Conclusions: 1.The present study demonstrated that chronic unpredicted stress induced the decrease of the new born neurons in the dentate gyrus of rat hippocampus.2.Running exercise protected the new born neurons in the dentate gyrus of hippocampus of the rats with their behavioral performance improvement.3.Running exercise-induced improvement of the new born neurons in the dentate gyrus of hippocampus might be an important reason for exercise against depression,and these results might provide an important quantitative basis for further exploring the mechanism of depression and new efficient treatment of depression.PART THREE THE CHANGES OF OLIGODENDROCYTE PROGENITOR CELLS IN DEFFERENT SUBREGIONS OF HIPPOCAMPUS IN DEPRESSION MODEL RATS AND THE EFFECT OF RUNNING EXERCISE ON OLIGODENDROCYTE PROGENITOR CELLS IN DEFFERENT SUBREGIONS OF HIPPOCAMPUS IN DEPRESSION MODEL RATSObjective : To investigate the changes of the oligodendrocyte progenitor cells in different hippocampal subregions in chronic unpredicted stress model rats,as well as the effect of running exercise on the oligodendrocyte progenitor cells in different hippocampal subregions of depression model rats,in order to investigate the proliferation and differentiation of the oligodendrocyte progenitor cells in the mechanism of depression and the antidepression of running exercise.Methods: In the current study,we used behavioral mechods,immunohistochemistry technique and stereological method to investigate the changes of the oligodendrocyte progenitor cells in the dentate gyrus,CA1 subregion and CA3 subregion in hippocampus of depression model rats and the effect of running exercise on the oligodendrocyte progenitor cells of different hippocampal subregions in depression model rats.The Sprague-Dawley rats were adminstered 7-week chronic unpredicted stress and following 6-week running exercise.After the behavioral tests,the immunohistochemistry staining and stereological quantification of the oligodendrocyte progenitor cells of different hippocampal subregions in three groups were done,respectively.Results: After 7-week chronic unpredicted stress,the total number of the Olig2+ glia were significantly reduced in both dentate gyrus and CA3 subregion of hippocampus in the model control group,when compared to that in unstressed control group(p>0.05).After 7-week chronic unpredicted stress,the total number of the NG2+ glia were significantly decreased in dentate gyrus,CA1 subregion and CA3 subregion of hippocampus in the model control group,when compared to that in unstressed control group(p>0.05).Following the 6 weeks of exercise,the total number of the Olig2+ glia in the dentate gyrus of hippocampus was significantly increased in the running model group,when compared to that in model control group(p<0.05),but there was no significant difference in the number of Olig2+ glia in CA1 subregion and CA3 subregion between model control group and running model group(p>0.05).There were no significant changes of Olig2+ glia in dentate gyrus,CA1 subregion and CA3 subregion between unstressed control group and running model group(p>0.05).After 6 weeks of exercise schedule,the total number of the NG2+ glia in the dentate gyrus was significantly increased when compared to that in model control group(p<0.05),but there were no significant differences of the total number of NG2+ glia in CA1 subregion and CA3 subregion between model control group and running model group(p>0.05).However,the total number of NG2+ glia in dentate gyrus,CA1 subregion and CA3 subregion in running model group was still significantly less than that in unstressed control group(p<0.05).Conclusions: 1.The present study showed that the decrease of olig2+ glia and NG2+ glia were observed in different hippocampal subregions of depression model rats.2.Running exercise only protected the olig2+ glia and NG2+ glia in the dentate gyrus of rat hippocampus,which indicated the dentate gyrus might be a important brain area in the mechanism of antidepression.3.Running exercise improved the proliferation and differentiation of the oligodendrocyte progenitor cells in the dentate gyrus of hippocampus,which might provide an important evidence for the possibility that the oligodendrocyte progenitor cell changes might be involved in the depression and antidepression of running exercise.