Objective: To investigate the role of aerobic exercise in inhibiting chronic unpredictable mild stress (CUMS) depressed mice hippocampal inflammatory response and its potential mechanisms. Methods: Fifty-four male eight-week-old C57BL/6 mice were divided as control group (CG) (18 mice) and model group (36 mice). Model group mice were treated with 13 chronic stimulating factors for 28 days to set up the CUMS depression model. Neurobehavioral assessment was performed after modeling. The mice in the model group were randomly divided into the control model group (MG) and the aerobic exercise group (EG), with 18mice in each group. The EG group carried out the adaptive training of the running platform: 10 m/min, 0° slope, and increased by 10 minutes per day for 6 days. The formal training was carried for 8 weeks with 10 m/min speed, 0° slope, 60 min/d, 6 d/Week. After the training, a neurobehavioral assessment was performed, and hippocampus IL-1β and IL-10 protein levels were detected by ELISA. RT–PCR was used to detect the expression of miR-223 and TLR4, MyD88, and NF-κB in the hippocampus. Western blot was used to detect the expression of TLR4 and phosphorylated NF-κBp65 protein in the hippocampus. Results: The hippocampus function of CUMS depression model mice was impaired. The forced swimming and forced tail suspension time were significantly prolonged, and inflammatory factors IL-1β were significantly increased in the hippocampus. Aerobic exercise significantly improves CUMS-depressed mice hippocampal function, effectively reducing depressive behavior and IL-1β levels, and increasing IL-10 levels. Besides, aerobic exercise significantly upregulates the expression level of miR-223 and inhibits the high expression of TLR4, MyD88, and NF-κB. Conclusion: Aerobic exercise significantly increases the CUMS-depressed mice hippocampus expression of miR-223, and inhibits the downstream TLR4/MyD88-NF-κB signaling pathway and the hippocampal inflammatory response, which contributes to the improvement of the hippocampal function.

This thesis was to investigate the protective effect and mechanism of H2S-mediated aerobic exercise on the antagonism of the hippocampus inflammatory response in CUMS-depressed mice. Seventy C57BL/6 mice were randomly divided into control group (CG), model control group (MG), model exercise group (ME), H2S enhanced group (HG) and H2S enhanced and exercise group (HE). All mice except CG underwent a 28-day CUMS depression model. ME and HE received moderate-intensity aerobic treadmill training for 8 weeks. They were randomly selected for Nissl staining, Immunofluorescence, methylene blue colorimetric assay, and ELISA. The levels of IL-10 and TNF-ɑ were detected by qRT-PCR, and the expression levels of CBS and inflammatory-related factors in the hippocampus were detected. Compared with CG, the number of erections, modifications, and crossing grids in MG mice were significantly reduced, the time of forced swimming and forced tail suspension was significantly prolonged, the positive rate of 5-HT decreased, and the symptoms of depression were obvious. The positive rate of CD45+ increased, the inflammatory response was obvious, and the content of H2S and the expression of biosynthetic enzyme CBS decreased. Aerobic exercise and H2S-enhanced mice improved depressive symptoms, decreased proinflammatory factors, increased anti-inflammatory factors, increased H2S content, increased CBS expression, and increased H2S. H2S may participate in aerobic exercise to antagonize the inflammatory process of the hippocampus in CUMS-depressed mice by reducing the release of inflammatory response factors and hippocampus nerve injury factors, and effectively alleviate inflammatory injury in the hippocampus of depressed mice.

This study was to study the impact of aerobic exercises on the chronic unpredictable mild stress (CUMS) in mice, and to discuss the possible mechanism from the skeletal muscle AMPK/PGC-1α energy metabolism signaling pathway. The healthy male mice were randomly divided into Control Group (CG), Model Group (MG), and Model Exercise Group (ME).Twelve stress methods were adopted for four weeks (28 days) to establish the depression model. ME was subject to aerobic training plan after the model was established. The weight of the mice was recorded weekly. After the experimental intervention, the three groups of mice were subjected to behavioral assessment tests. Western blotting, RT-PCR, and ELISA were performed to test AMPK, p-AMPK, PGC-1α, and ATP in skeletal muscle. There were no significant difference in body weight between the three groups. CUMS leaded to significant decline in behavioral scores. and the p-AMPK and PGC-1α decreased significantly. But boosted ATP content. Aerobic exercise enhanced the expressions of p-AMPK and PGC-1α, increased the ratio of p-AMPK/AMPK, boosted ATP content. And improved behavioral scores significantly. Chronic stress-induced depression-like behavior was improved significantly by Aerobic exercise. The mechanism of aerobic exercise for improving depressive symptoms in mice with chronic stress depression may be related to influence AMPK/PGC-1α pathway.

This study examined how aerobic exercise affect the IL-33/ST2-MyD88 signaling pathway in mice with chronic unpredictable mild stress (CUMS) induced depression METHOD: Thirty-six C57BL/6 mice were randomly assigned t three groups: a control group (CG), a model group (MG), and an exercise group (ME). We created a depression model using chronic unpredictable mild stress, after which the ME group underwent 8 weeks of aerobic training. After exercise intervention, neurobehavioral assessment was performed. ELISA was used to detect the levels of IL-33, IL-1β and IL-10 in the serum of mice. Toluidine blue Nissl staining was used to observe the structure of hippocampal neurons. Total RNA was extracted from blood samples using magnetic beads and from hippocampal tissue or neurons using Trizol. The levels of IL-33, ST2, MyD88, IL-1β, IL-10 and NF-κB mRNA in mice were detected by RT-PCR RESULT: The number of lattice crossings and modification times were significantly reduced in MG group, the exercise time was significantly shortened, and the sugar and water preference index was significantly reduced, while the immobility time in forced swimming and tail suspension tests were significantly prolonged. The results indicated that CUMS successfully induced anhedonia and depression-like behaviors in the mice. In the ME group, there was a significant increase in the number of crossing lattices, modification times, exercise duration, and sugar and water preference index, while the immobility time in the forced swimming and tail suspension tests significantly decreased. Compared with the CG group, serum levels of inflammatory factors IL-33, IL-1β, and NF-κB significantly increased in the MG group, while these levels significantly decreased in the ME group. It decreased and IL-10 showed a very significant increase. Nissl staining results indicated that hippocampal nerve cells in MG group were sparsely arranged, with widened gaps, severe nucleus contraction, and shallow staining. The ME group had reduced neuronal vacuoles and improved nuclear shrinkage. Immunohistochemical results revealed that in MG group, the expression of pro-inflammatory factors IL-1β and MyD88 increased. In Contrast, the ME group exhibited a decrease in IL-1β and MyD88, alongside a significant increase in the anti-inflammatory factor IL-10. In the RT-PCR test results, the blood inflammation signal pathway IL-33/ST2 and its downstream factors MyD88, NF-κB, and IL-1β mRNA were significantly up-regulated, and the inhibitory factor IL-10 mRNA was up-regulated in MG group. Gene expression trends for IL-33 mRNA, ST2 mRNA, IL-1β mRNA, MyD88 mRNA and NF-κB mRNA in hippocampus tissue were similar to those in blood, all showing significant up-regulation. In contrast, IL-10 mRNA did not exhibit significant up-regulation. While IL-33/ST2 expression did not significantly decrease, other pro-inflammatory factors showed significant down-regulation, and anti-inflammatory factors demonstrated significant up-regulated. Similarly, IL-33 mRNA, ST2 mRNA and MyD88 mRNA expressions in the hippocampus of ME mice mirrored the changes observed in blood when compared to MG mice. NF-κB mRNA was significantly down-regulated, while IL-1β mRNA showed no significant change, and IL-10 mRNA was up-regulated, albeit not significantly. Aerobic exercise may counteract the CUMS depression model in mice by regulating the IL-33/ST2-MyD88 signaling pathway. The strong correlation of inflammatory cytokines between blood and hippocampus indicated that assessing inflammatory damage in the hippocampus could be done through blood tests of the signaling pathway and related cytokine levels.