Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats
A typical enriched environment (EE), which combines physical activity and social interaction, has been proven to mitigate cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, it remains unclear how the different components of EE promote cognitive recovery after CCH. This stu...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923024000303 |
| _version_ | 1797281188026515456 |
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| author | Bin Fan Ying Zhang Qihang Luo Chizi Hao Weijing Liao |
| author_facet | Bin Fan Ying Zhang Qihang Luo Chizi Hao Weijing Liao |
| author_sort | Bin Fan |
| collection | DOAJ |
| description | A typical enriched environment (EE), which combines physical activity and social interaction, has been proven to mitigate cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, it remains unclear how the different components of EE promote cognitive recovery after CCH. This study stripped out the different components of EE into physical environmental enrichment (PE) and social environmental enrichment (SE), and compared the neuroprotective effects of PE, SE and typical EE (PSE) in CCH. The results of novel object recognition and Morris water maze tests showed that PE, SE, and PSE improved cognitive function in CCH rats. Additionally, Nissl and TUNEL staining revealed that three EEs reduced neuronal loss in the hippocampus. PSE exhibited superior neuroprotective and functional improvement effects compared to PE and SE, while there was no significant difference between PE and SE. Furthermore, three EEs reduced lipid peroxidation in the hippocampus with decreasing the levels of MDA and increasing the activities of SOD and GSH. The expression of SLC7A11 and GPX4 was increased, while the level of p53 was reduced in three EEs. This suggested that three EEs inhibited ferroptosis by maintaining the redox homeostasis in the hippocampus. Three EEs reduced the levels of IL-β, TNF-α, and IL-6, thereby inhibiting neuroinflammation. Additionally, Western blotting and immunofluorescence results indicated that three EEs also inhibited the TLR4/MyD88/p38MAPK signaling pathway. These findings collectively demonstrated that the three EEs alleviated hippocampal ferroptosis and neuroinflammation in CCH rats, thereby reducing neuronal loss, which might be associated with the inhibition of the TLR4/MyD88/p38MAPK signaling pathway. Moreover, the study results supported that it is only through the combination of physical exercise and social interaction that the optimal neuroprotective effects can be achieved. These findings provided valuable insights for the prevention and treatment of vascular cognitive impairment. |
| first_indexed | 2024-03-07T16:53:52Z |
| format | Article |
| id | doaj.art-5a7d55133a134c09816848d199d327b4 |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-07T16:53:52Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-5a7d55133a134c09816848d199d327b42024-03-03T04:28:53ZengElsevierBrain Research Bulletin1873-27472024-03-01208110897Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion ratsBin Fan0Ying Zhang1Qihang Luo2Chizi Hao3Weijing Liao4Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaCorrespondence to: #169, East Lake Road, Wuchang District, Wuhan, China.; Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaCorrespondence to: #169, East Lake Road, Wuchang District, Wuhan, China.; Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaA typical enriched environment (EE), which combines physical activity and social interaction, has been proven to mitigate cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, it remains unclear how the different components of EE promote cognitive recovery after CCH. This study stripped out the different components of EE into physical environmental enrichment (PE) and social environmental enrichment (SE), and compared the neuroprotective effects of PE, SE and typical EE (PSE) in CCH. The results of novel object recognition and Morris water maze tests showed that PE, SE, and PSE improved cognitive function in CCH rats. Additionally, Nissl and TUNEL staining revealed that three EEs reduced neuronal loss in the hippocampus. PSE exhibited superior neuroprotective and functional improvement effects compared to PE and SE, while there was no significant difference between PE and SE. Furthermore, three EEs reduced lipid peroxidation in the hippocampus with decreasing the levels of MDA and increasing the activities of SOD and GSH. The expression of SLC7A11 and GPX4 was increased, while the level of p53 was reduced in three EEs. This suggested that three EEs inhibited ferroptosis by maintaining the redox homeostasis in the hippocampus. Three EEs reduced the levels of IL-β, TNF-α, and IL-6, thereby inhibiting neuroinflammation. Additionally, Western blotting and immunofluorescence results indicated that three EEs also inhibited the TLR4/MyD88/p38MAPK signaling pathway. These findings collectively demonstrated that the three EEs alleviated hippocampal ferroptosis and neuroinflammation in CCH rats, thereby reducing neuronal loss, which might be associated with the inhibition of the TLR4/MyD88/p38MAPK signaling pathway. Moreover, the study results supported that it is only through the combination of physical exercise and social interaction that the optimal neuroprotective effects can be achieved. These findings provided valuable insights for the prevention and treatment of vascular cognitive impairment.http://www.sciencedirect.com/science/article/pii/S0361923024000303Environmental enrichmentPhysical activitySocial interactionChronic cerebral hypoperfusionFerroptosisNeuroinflammation |
| spellingShingle | Bin Fan Ying Zhang Qihang Luo Chizi Hao Weijing Liao Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats Brain Research Bulletin Environmental enrichment Physical activity Social interaction Chronic cerebral hypoperfusion Ferroptosis Neuroinflammation |
| title | Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats |
| title_full | Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats |
| title_fullStr | Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats |
| title_full_unstemmed | Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats |
| title_short | Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats |
| title_sort | physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of tlr4 myd88 p38mapk pathway in chronic cerebral hypoperfusion rats |
| topic | Environmental enrichment Physical activity Social interaction Chronic cerebral hypoperfusion Ferroptosis Neuroinflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0361923024000303 |
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