| Part one The effects of running exercise on the behaviors and hippocampal neuroinflammation of depression model rats induced by CUSObjective: Depression is a common mood disorder that seriously affects the patient’s quality of life.Running exercise has been shown to alleviate symptoms of depression,but the specific mechanism of antidepressant effects is still unclear.Hippocampal neuroinflammatory disorders play a critical role in the pathogenesis of depression.This study mainly explored the effects of running exercise on the behaviors and hippocampal neuroinflammation of CUS-induced depressed rats.Methods: 6-8 weeks old male Sprague-Dawley rats were randomly divided into the control group(n = 19)and the CUS intervention group(n = 100)after adaptive feeding,baseline adjustment of sucrose preference and screening.The rats in the CUS intervention group were exposed to CUS for 5 weeks.The sucrose preference test was used to evaluate the depressivelike behaviors of rats.33 model rats were screened out and classified as CUS group.Then,the CUS group rats were randomly divided into CUS + standard group(CUS + STD group,n = 16)and CUS + running group(CUS + RN group,n = 17).The rats in the CUS + RN group were given running exercise intervention for 6 weeks.The body weight of rats was measured during the fixed time per week.The sucrose preference test was used to evaluate the depressive-like behaviors and the elevated plus maze test was used to evaluate the anxiety-like behaviors.The mRNA levels and protein levels of inflammatory factors in the hippocampus of rats were detected with real-time quantitative PCR and ELISA,respectively.Results: 1.Before CUS intervention,there was no significant difference in the body weight between the CUS group rats and the control group rats(P > 0.05).After CUS intervention,the body weight of rats in the CUS group was significantly lower than that of the control group(P < 0.01).During the period of running exercise,the body mass of rats in the CUS + STD group and the CUS + RN group was significantly lower than that of the control group(P < 0.01,P < 0.01).2.Before the stress intervention,there was no significant difference in the percentage of sucrose preference between the CUS group and the control group(P > 0.05).After the 5-week CUS intervention,the percentage of sucrose preference of the CUS group was significantly decreased compared to the control group(P < 0.01).After 6 weeks of running exercise,the percentage of sucrose preference in the CUS + RN group was significantly higher than that of the CUS + STD group(P < 0.01).3.There were no significant differences in the total number of arm entry,the number of open arm entry,the residence time of open arm entry,the number of closed arm entry,the residence time of closed arm entry,the percentage of open arm entry and the percentage of residence time in the open arm among the control group,CUS + STD group and CUS + RN group(P > 0.05).4.The results of q RT-PCR showed that the mRNA levels of hippocampal inflammatory factors IL-1β and i NOS in the CUS + STD group were significantly higher than those in the control group(P < 0.01,P < 0.05).In addition,the mRNA level of IL-1β in the hippocampus of the CUS + RN group rats was significantly lower than that of the CUS + STD group(P < 0.05).There were no significant differences in the levels of mRNA level of IL-6 and TNF-α in the hippocampus of the three groups of rats(P > 0.05,P > 0.05).5.The results of ELISA showed that the protein levels of IL-1β and IL-6 in the hippocampus of rats in the CUS + STD group were significantly higher than those in the control group(P < 0.05,P < 0.05).Compared with rats in the CUS + STD group,the protein levels of IL-1β and IL-6 in the hippocampus of rats in the CUS + RN group were significantly decreased(P < 0.01,P < 0.01).In addition,the protein level of i NOS in the hippocampus of CUS + STD group was significantly higher than that of the control group(P < 0.05),but there was no significant difference in the protein level of TNF-α in the hippocampus of rats in the three groups(P > 0.05).Conclusions: 1.Running exercise could alleviate depressive-like behaviors in CUS-induced depression model rats.2.The levels of inflammatory factors in the hippocampus of CUS-induced depression model rats were increased,and running exercise could inhibit the expression of inflammatory factors in the hippocampus of depression model rats.Part two The effect of running exercise on hippocampal microglia of depression model rats induced by CUSObjective: Running exercise can relieve the depressive-like symptoms of depression model rats and inhibit the expression of inflammatory factors in the hippocampus of the model rats,but the cellular mechanism involved in antidepressant effect of running exercise remains to be elucidated.This study mainly explored the effect of running exercise on the total number of hippocampal microglia and activation of microglia in CUS-induced depression model rats.Methods: Five rats from each group were randomly selected from the part one and frozen sections of brain tissue were prepared.The total number of microglia in each subregion of the hippocampus of rats was accurately quantified using immunohistochemical technique and stereological method.The immunofluorescence method combined with laser confocal technology was used to evaluate the density and proportion of activated microglia in each subregion of the hippocampus in each group of rats.Results: 1.The stereological results showed that the number of Iba1~+ cells in the CA1,CA2/3 and DG of the CUS + STD group rats was significantly higher than that of the control group rats(P < 0.01,P < 0.01,P < 0.01).After 6 weeks of running exercise,compared with rats in the CUS + STD group,the number of Iba1~+ cells in the CA1,CA2/3 and DG of the CUS + RN group rats was significantly decreased(P < 0.01,P < 0.01,P < 0.05).2.The results of immunofluorescence showed that the density of Iba1~+/CD68~+ cells and the proportion of Iba1~+/CD68~+ cells in Iba1~+ cells in the CA1,CA2/3 and DG of the CUS + STD group rats were significantly increased compared with the control group(P < 0.01,P < 0.01,P < 0.01;P < 0.05,P < 0.01,P < 0.01).In addition,the density of Iba1~+/CD68~+ cells and the proportion of Iba1~+/CD68~+ cells in Iba1~+ cells in the DG subregion of rats in the CUS + RN group were decreased(P < 0.01,P < 0.01).However,There were no significant differences in the density of Iba1~+ cells and the proportion of Iba1~+/CD68~+ cells in Iba1~+ cells in the CUS + RN group compared with the CUS + STD group(P > 0.05,P > 0.05;P > 0.05,P > 0.05).Conclusions: 1.The total number of microglia in the CA1,CA2/3 and DG of the hippocampus in depression model rats was significantly increased,and running exercise had a significant improvement effect on these changes.2.The activation of microglia in the CA1,CA2/3 and DG of the hippocampus in depression model rats was enhanced,and running exercise significantly inhibited the activation of the microglia in the hippocampal DG area of the model rats.3.The effect of running exercise on hippocampal microglia in depression model rats might be one of the important mechanisms for improving depression symptoms and inhibiting the expression of inflammatory factors in the hippocampus. |
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