| Objective:to investigate the effects of aerobic exercise on hippocampal inflammation in CUMS rats after 4 weeks of Chronic unforeseeable mild stress(CUMS)induced depression-like behavior.Methods:48 3-month-old male SPF SD rats were randomly divided into 4 groups(n=12):blank control group(C),depression model group(D),depression+swimming group(E1)and post-depression swimming group(E2).Each group received CUMS stimulation for 4 weeks for different experimental purposes and swimming intervention for 4 weeks at different stages.After the completion of modeling,the whole brain 5-HT and NE were tested by sugar water consumption test(SPT),open field test(OFT)and ELISA to verify the success of the CUMS model.Real-time PCR,Western Blotting,immunofluorescence(IF)and HE staining were used to observe the expression of hippocampal morphological structure and related indicators in rats.Results:(1)general condition:group C,stable mood,active and healthy,smooth hair,normal diet,granular stool.Group D was irritable and aggressive,with decreased food intake,hair loss,emaciated body,and shapeless stool.The status of group E1 and E2 was slightly worse than that of group C.(2)weight gain:before modeling,there was no difference in weight gain in each group(P>0.05).After modeling,the weight gain of group D,E1 and E2 was significantly lower than that of group C(P<0.01),and the weight gain of group E1 after exercise intervention was significantly higher than that of group C,D and E2(P<0.01),while that of group E2 was significantly lower than that of group C and D(P<0.01).(3)SPT:there was no significant difference in the total amount of drinking water in each group(P>0.05).The white water consumption of group D,E1 and E2 was significantly higher than that of group C(P<0.01),while that of group E1 and E2 was significantly lower than that of group D(P<0.01),and that of group E2 was significantly higher than that of group E1(P<0.05).The consumption of sugar water in group D and E2 was significantly lower than that in group C(P<0.01)(P<0.05),and that in group E1 and E2 was significantly higher than that in group D(P<0.01).The sugar water consumption ratio of group D,E1 and E2 was significantly lower than that of group C(P<0.01),and that of group E1 and E2 was significantly higher than that of group D(P<0.01).(4)OFT:the activity of group D,E1 and E2 was significantly lower than that of group C(P<0.01),and that of group E1 and E2 was significantly higher than that of group D(P<0.01).The total distance of group D and E2 was significantly lower than that of group C and group E1(P<0.01)(P<0.05).The average speed of group D and E2 was significantly lower than that of group C and group E1(P<0.01)(P<0.05).The central region time of group C,E1 and E2 was significantly higher than that of group D(P<0.01),and that of group E2 was significantly higher than that of group C(P<0.05).The central region distance of group C,E1 and E2 was significantly higher than that of group D(P<0.01).(5)ELISA:the content of whole brain 5-HT in group C,E1 and E2 was significantly higher than that in group D(P<0.01).The NE content of whole brain in group D and E2 was significantly lower than that in group C(P<0.01),and that in group E1 and E2 was significantly higher than that in group D(P<0.01).(6)RT-PCR:the expression of IL-1? mRNA in group C,E1 and E2 was significantly higher than that in group D(P<0.01).The expression of IL-10 mRNA in group C,E1 and E2 was significantly higher than that in group D(P<0.01),while that in group E1 and E2 was significantly higher than that in group C(P<0.01),and that in group E1 was significantly higher than that in group E2(P<0.01).The mRNA expression of GFAP in group D and E2 was significantly lower than that in group C and E1(P<0.01).CD11b mRNA expression in E1 and E2 groups was significantly lower than that in D group(P<0.01).(7)the expression of IL-1?protein in WB:D group was significantly higher than that in C,E1 and E2 groups(P<0.01).The expression of IL-10 protein in group D was significantly lower than that in group C,E1 and E2(P<0.01).The expression of GFAP protein in group D was significantly lower than that in group C,E1 and E2(P<0.01).CD11b protein expression in group D was significantly higher than that in group C,E1 and E2(P<0.01).There was no significant difference in the expression of related proteins in the hippocampus in groups C,E1 and E2(P>0.05).(8)IF:the IL-1?IOD value of group C,E1 and E2 was significantly higher than that of group D(P<0.01)(P<0.05),and there was no significant difference between groups C,E1 and E2(P>0.05).The IL-10 IOD value of group C,E1 and E2 was significantly higher than that of group D(P<0.01)(P<0.05),and there was no significant difference between groups C,E1 and E2(P>0.05).(9)HE:the DG neurons in the hippocampus of group C were abundant,and the neurons were closely arranged and orderly.Group D had the least number of DG neurons in the hippocampus,and the neurons were loosely arranged and in disordered order.The neurons in the DG region of the hippocampus in the E1 and E2 groups were more numerous but less than those in the C group,and the neurons were closely arranged and orderly.(10)correlation analysis:IL-1? expression was negatively correlated with the central region time(r=-0.579,P<0.01),and was highly negatively correlated with the sugar-water consumption ratio(r=-0.702,P<0.01).The expression of IL-10 protein was positively correlated with the time height of the central region(r=0.632,P<0.01)and the sugar water consumption ratio(r=0.753,P<0.01).The expression of IL-1?mRNA was negatively correlated with the time height in the central region(r=-0.648,P<0.05),and negatively correlated with the sugar water consumption ratio(r=-0.623,P<0.05).The expression of IL-10 mRNA was positively correlated with the time height of the central region(r=0.640,P<0.01),and positively correlated with the sugar-water consumption ratio(r=0.508,P<0.01).Conclusion:(1)after 4 weeks of CUMS stimulation,the rats showed general state deterioration,slow weight gain,loss of interest in reward mechanism and new things,and decreased expression of 5-HT and NE in the whole brain.(2)CUMS stimulation at 4 weeks up-regulated expression of IL-1? and CD11b in the hippocampus of rats,and decreased expression of IL-10 and GFAP,suggesting that the activation of neuroinflammation may be one of the mechanisms leading to depressive-like behavior.(3)aerobic exercise during and after CUMS stimulation reduced the expression of IL-1? and CD11b in hippocampus of CUMS rats,while the expression of IL-10 and GFAP were up-regulated.This suggests that regular aerobic exercise can effectively relieve depression-like behavior caused by central inflammation.This suggests that the improvement of central inflammation may be one of the neurobiological mechanisms for alleviating depression-like behavior.(4)the decrease of time in the central field and the decrease of sugar-water consumption ratio in CUMS rats was associated with the increased expression of IL-1?mRNA and IL-1?mRNA in hippocampus and the decreased expression of IL-10 mRNA and IL-10 mRNA.The expression of IL-1?and IL-10 in hippocampus was associated with depression-like behavior. |
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