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Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway

Traumatic brain injury (TBI) is a universal leading cause of long-term neurological disability and causes a huge burden to an ever-growing population. Moderate intensity of treadmill exercise has been recognized as an efficient intervention to combat TBI-induced motor and cognitive disorders, yet th...

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Autores principales: Chen, Jie, Zhu, Tong, Yu, Dongyu, Yan, Bing, Zhang, Yuxiang, Jin, Jungong, Yang, Zhuojin, Zhang, Bao, Hao, Xiuli, Chen, Zhennan, Yan, Chunxia, Yu, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415513/
https://www.ncbi.nlm.nih.gov/pubmed/37193866
http://dx.doi.org/10.1007/s12035-023-03379-8
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author Chen, Jie
Zhu, Tong
Yu, Dongyu
Yan, Bing
Zhang, Yuxiang
Jin, Jungong
Yang, Zhuojin
Zhang, Bao
Hao, Xiuli
Chen, Zhennan
Yan, Chunxia
Yu, Jun
author_facet Chen, Jie
Zhu, Tong
Yu, Dongyu
Yan, Bing
Zhang, Yuxiang
Jin, Jungong
Yang, Zhuojin
Zhang, Bao
Hao, Xiuli
Chen, Zhennan
Yan, Chunxia
Yu, Jun
author_sort Chen, Jie
collection PubMed
description Traumatic brain injury (TBI) is a universal leading cause of long-term neurological disability and causes a huge burden to an ever-growing population. Moderate intensity of treadmill exercise has been recognized as an efficient intervention to combat TBI-induced motor and cognitive disorders, yet the underlying mechanism is still unclear. Ferroptosis is known to be highly implicated in TBI pathophysiology, and the anti-ferroptosis effects of treadmill exercise have been reported in other neurological diseases except for TBI. In addition to cytokine induction, recent evidence has demonstrated the involvement of the stimulator of interferon genes (STING) pathway in ferroptosis. Therefore, we examined the possibility that treadmill exercise might inhibit TBI-induced ferroptosis via STING pathway. In this study, we first found that a series of ferroptosis-related characteristics, including abnormal iron homeostasis, decreased glutathione peroxidase 4 (Gpx4), and increased lipid peroxidation, were detected at 44 days post TBI, substantiating the involvement of ferroptosis at the chronic stage following TBI. Furthermore, treadmill exercise potently decreased the aforementioned ferroptosis-related changes, suggesting the anti-ferroptosis role of treadmill exercise following TBI. In addition to alleviating neurodegeneration, treadmill exercise effectively reduced anxiety, enhanced spatial memory recovery, and improved social novelty post TBI. Interestingly, STING knockdown also obtained the similar anti-ferroptosis effects after TBI. More importantly, overexpression of STING largely reversed the ferroptosis inactivation caused by treadmill exercise following TBI. To conclude, moderate-intensity treadmill exercise rescues TBI-induced ferroptosis and cognitive deficits at least in part via STING pathway, broadening our understanding of neuroprotective effects induced by treadmill exercise against TBI.
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spelling pubmed-104155132023-08-12 Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway Chen, Jie Zhu, Tong Yu, Dongyu Yan, Bing Zhang, Yuxiang Jin, Jungong Yang, Zhuojin Zhang, Bao Hao, Xiuli Chen, Zhennan Yan, Chunxia Yu, Jun Mol Neurobiol Article Traumatic brain injury (TBI) is a universal leading cause of long-term neurological disability and causes a huge burden to an ever-growing population. Moderate intensity of treadmill exercise has been recognized as an efficient intervention to combat TBI-induced motor and cognitive disorders, yet the underlying mechanism is still unclear. Ferroptosis is known to be highly implicated in TBI pathophysiology, and the anti-ferroptosis effects of treadmill exercise have been reported in other neurological diseases except for TBI. In addition to cytokine induction, recent evidence has demonstrated the involvement of the stimulator of interferon genes (STING) pathway in ferroptosis. Therefore, we examined the possibility that treadmill exercise might inhibit TBI-induced ferroptosis via STING pathway. In this study, we first found that a series of ferroptosis-related characteristics, including abnormal iron homeostasis, decreased glutathione peroxidase 4 (Gpx4), and increased lipid peroxidation, were detected at 44 days post TBI, substantiating the involvement of ferroptosis at the chronic stage following TBI. Furthermore, treadmill exercise potently decreased the aforementioned ferroptosis-related changes, suggesting the anti-ferroptosis role of treadmill exercise following TBI. In addition to alleviating neurodegeneration, treadmill exercise effectively reduced anxiety, enhanced spatial memory recovery, and improved social novelty post TBI. Interestingly, STING knockdown also obtained the similar anti-ferroptosis effects after TBI. More importantly, overexpression of STING largely reversed the ferroptosis inactivation caused by treadmill exercise following TBI. To conclude, moderate-intensity treadmill exercise rescues TBI-induced ferroptosis and cognitive deficits at least in part via STING pathway, broadening our understanding of neuroprotective effects induced by treadmill exercise against TBI. Springer US 2023-05-16 2023 /pmc/articles/PMC10415513/ /pubmed/37193866 http://dx.doi.org/10.1007/s12035-023-03379-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chen, Jie
Zhu, Tong
Yu, Dongyu
Yan, Bing
Zhang, Yuxiang
Jin, Jungong
Yang, Zhuojin
Zhang, Bao
Hao, Xiuli
Chen, Zhennan
Yan, Chunxia
Yu, Jun
Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway
title Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway
title_full Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway
title_fullStr Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway
title_full_unstemmed Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway
title_short Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway
title_sort moderate intensity of treadmill exercise rescues tbi-induced ferroptosis, neurodegeneration, and cognitive impairments via suppressing sting pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415513/
https://www.ncbi.nlm.nih.gov/pubmed/37193866
http://dx.doi.org/10.1007/s12035-023-03379-8
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