The Positive Effects Of Running Exercise On Hippocampal Astrocytes In A Rat Model Of Depression

Part one The study of the hippocampal astrocytes in the rat model of depression induced by chronic unpredictable stressObjective Astrocyte is the predominant cell type in the brain and performs key functions vital to central nervous system(CNS)physiology.Mounting evidences suggest that astrocyte changes are closely associated with mental disorders.In order to study the changes of astrocytes in depression,we used the chronic unpredictable stress(CUS)depression rat model to investigate the changes in the number of astrocytes in the hippocampus.Methods Sixty adult male Sprague-Dawley(SD)rats were randomly divided into the control group and the depression model group after adaptive feeding 2 weeks,and the depression model group was subjected to chronic stress for 5 weeks.The sucrose preference test(SPT)was used to assess anhedonia of rats.Then,15 depressed rats were selected as the CUS group and 15 normal rats were selected as the control group.Five rats of each group were randomly selected to be used in the first part.Total hippocampal volume and each hippocampal subregion volume were measured.Immunohistochemistry and modern stereological methods were used to precisely quantify the total number of glial fibrillary acidic protein(GFAP)+ astrocytes in the hippocampus,and immunofluorescence was used to quantify the density of bromodeoxyuridine(Brd U)+ and GFAP+ cells in the hippocampus.Results 1.Body weights: There was no significant difference in the body weights in the control group and the CUS group.During the period of CUS intervention,the body weight of the rats in the CUS group was significantly lower than that of the rats in the control group(p < 0.05).2.SPT: There was no significant difference in the sucrose preference in the control group and the CUS group.After 5 weeks of CUS intervention,the sucrose preference of the rats in the CUS group was significantly lower than that of the rats in the control group(p < 0.05).3.Hippocampal volume: After 5 weeks of CUS intervention,the total hippocampal volume,the volumes of CA1 and DG region of the rats in the CUS group were significantly lower than those of the rats in the control group(p < 0.05,p < 0.05,p < 0.05),but there was no significant difference in the volume of the CA2/3 region between the CUS group and the control group.4.The number of astrocytes: After 5 weeks of CUS intervention,the number of GFAP+ astrocytes in the CA1 and DG region in the CUS group was significantly lower than that in the control group(p < 0.05,p < 0.05),but the number of GFAP+ astrocytes in the CA2/3 region was not significantly different between the CUS group and the control group.5.The density of newborn astrocytes: After 5 weeks of CUS intervention,the density of Brd U+ cells in the CA1 and CA2/3 region in the CUS group was significantly lower than that in the control group(p < 0.05,p < 0.05),but the density of Brd U+ cells in the DG region was not significantly different between the CUS group and the control group.After the 5 weeks of CUS intervention,the density of GFAP+ cells in the CA1 and DG region in the CUS group was significantly lower than that in the control group(p < 0.05,p < 0.05),but the density of GFAP+ cells in the CA2/3 region was not significantly different between the CUS group and the control group.After the 5 weeks of CUS intervention,the density of Brd U+/GFAP+ cells in the CA1 and DG region in the CUS group was significantly lower than that in the control group(p < 0.05,p < 0.05),but the density of Brd U+/GFAP+ cells in the CA2/3 region was not significantly different between the CUS group and the control group.Conclusions 1.The decrease of sucrose preference of rats in the CUS group indicated that our depression animal model was successfully established.2.Five weeks of CUS intervention reduced the total hippocampal volume and the volumes of CA1 and DG region not CA2/3.3.The number of astrocytes and newborn astrocytes were decreased in the CA1 and DG region in depression rat model.These findings suggested that the astrocytes and the newborn astrocytes in the CA1 and DG region might play a vital role in the pathogenesis of depression,which might provide important structural bases for exploring the pathogenesis of depression.Part two The positive effects of running exercise on hippocampal astrocytes in a rat model of depressionObjective Running exercise has been shown to alleviate depressive symptoms,but the mechanism of its antidepressant effect is still unclear.In order to study the mechanism of running exercise in depression,we used the chronic unpredictable stress(CUS)depression rat model to investigate the changes in the number of the astrocytes in the hippocampus after running exercise.Methods Adult male Sprague-Dawley(SD)rats were randomly divided into the control group and the depression model group,and the depression model group was subjected to chronic stress for 5 weeks.The sucrose preference test(SPT)was used to assess anhedonia of rats.Then,15 normal rats were selected as the control group,15 depressed rats were selected as the CUS/standard group and 15 depressed rats were selected as the CUS/running group.The CUS/running group was subjected running exercise for 6 weeks: 20 min per day,5 days per week.During this period,the control group and the CUS/standard group were not subjected to running exercise.Then,5 rats of each group were randomly selected.Total hippocampal volume and each hippocampal subregion volume were measured.Immunohistochemistry and modern stereological methods were used to precisely quantify the total number of glial fibrillary acidic protein(GFAP)+ astrocytes in the hippocampus,and immunofluorescence was used to quantify the density of bromodeoxyuridine(Brd U)+ and GFAP+ cells in the hippocampus.Results 1.Body weights: During the period of running exercise,the body weights of the rats in the CUS/standard group and the CUS/running group were significantly lower than that of the rats in the control group(p < 0.05,p < 0.05),but there was no significant difference in the body weights in the CUS/standard group and the CUS/running group.2.SPT: After 6 weeks of running exercise,the sucrose preference of the rats in the CUS/standard group was significantly lower than that of the rats in the control group(p < 0.05),and the sucrose preference in the CUS/running group was significantly higher than that in the CUS/standard group(p < 0.05).3.Hippocampal volume: After 6 weeks of running exercise,the total hippocampal volume,the volumes of CA1 and DG region of the rats in the CUS/standard group were significantly lower than those of the rats in the control group(p < 0.05,p < 0.05,p < 0.05),the total hippocampal volume,the volume of each hippocampal subregion of the rats in the CUS/running group were significantly higher than those of the rats in the CUS/standard group(p < 0.05,p < 0.05,p < 0.05,p < 0.05).4.The number of astrocytes: After 6 weeks of running exercise,the number of GFAP+ astrocytes in the CA1 and DG region in the CUS/standard group was significantly lower than that in the control group(p < 0.05,p < 0.05),the number of GFAP+ astrocytes in the each hippocampal subregion in the CUS/running group was significantly higher than that in the CUS/standard group(p < 0.05,p < 0.05,p < 0.05).5.The density of newborn astrocytes: After 6 weeks of running exercise,the density of Brd U+ cells in the CA1 and CA2/3 region in the CUS/standard group was significantly lower than that in the control group(p < 0.05,p < 0.05),and the density of Brd U+ cells in the each hippocampal subregion in the CUS/running group was significantly higher than that in the CUS/standard group(p < 0.05,p < 0.05,p < 0.05).After 6 weeks of running exercise,the density of GFAP+ cells in the CA1 and DG region in the CUS/standard group was significantly lower than that in the control group(p < 0.05,p < 0.05),and the density of GFAP+ cells in the each hippocampal subregion in the CUS/running group was significantly higher than that in the CUS/standard group(p < 0.05,p < 0.05,p < 0.05).After 6 weeks of running exercise,the density of Brd U+/GFAP+ cells in the CA1 and DG region in the CUS/standard group was significantly lower than that in the control group(p < 0.05,p < 0.05),and the density of Brd U+/GFAP+ cells in each hippocampal subregion in the CUS/running group was significantly higher than that in the CUS/standard group(p < 0.05,p < 0.05,p < 0.05).Conclusions 1.These results further confirmed that running exercise alleviated depressive symptoms.2.Running exercise significantly increased the total hippocampal volume and the volume of each hippocampal subregion in depressed rats.3.Six weeks of running exercise protected hippocampal astrocyte and its newborn in depressed rats.These findings suggested that the positive effects of running exercise on astrocytes and the generation of new astrocytes in the hippocampus might be important structural bases for the antidepressant effects of running exercise.