SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic Flux
This study explores the neuroprotective effects of resveratrol (Resv) against tri-o-cresyl phosphate (TOCP)-induced neurotoxicity in the spinal cord of adult hens. It is well documented that TOCP exposure causes significant neurodegeneration via mechanisms that involve endoplasmic reticulum (ER) str...
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2024-11-01
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| author | Xiangsheng Tian Yiquan Ou Shengyuan Shi Qiuhua Zhou Sihong Long Yao Xiang Weichao Zhao Dingxin Long |
| author_facet | Xiangsheng Tian Yiquan Ou Shengyuan Shi Qiuhua Zhou Sihong Long Yao Xiang Weichao Zhao Dingxin Long |
| author_sort | Xiangsheng Tian |
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| description | This study explores the neuroprotective effects of resveratrol (Resv) against tri-o-cresyl phosphate (TOCP)-induced neurotoxicity in the spinal cord of adult hens. It is well documented that TOCP exposure causes significant neurodegeneration via mechanisms that involve endoplasmic reticulum (ER) stress and impaired autophagy. In this experiment, adult hens were assigned to one of four groups: Control, Resv, TOCP, and TOCP + Resv. The spinal cord tissues were examined through transmission electron microscopy, hematoxylin and eosin (HE) staining, Nissl staining, and Western blotting to evaluate key proteins associated with ER stress and autophagy. Additionally, RT-qPCR and immunofluorescence were employed to measure sirtuin1 (SIRT1) expression. The findings revealed that TOCP induced severe ultrastructural damage, including disrupted myelin sheaths, dilated ER, and extensive neurodegeneration, as confirmed by histological evaluations. The expression levels of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, Beclin-1, P62, and LC3-II were also significantly elevated by TOCP. However, Resv treatment markedly attenuated these pathological changes by reducing ER stress, restoring autophagic flux, and upregulating SIRT1 expression, preserving spinal cord integrity. These results indicate that Resv can effectively counteract TOCP-induced neurotoxicity by modulating ER stress and autophagy, underscoring its potential as a therapeutic agent for neuroprotection. |
| format | Article |
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| institution | OA Journals |
| issn | 2305-6304 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Toxics |
| spelling | doaj-art-4abeab1193b04a90ae4e4cce7fd4213a2025-08-20T02:27:40ZengMDPI AGToxics2305-63042024-11-01121181010.3390/toxics12110810SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic FluxXiangsheng Tian0Yiquan Ou1Shengyuan Shi2Qiuhua Zhou3Sihong Long4Yao Xiang5Weichao Zhao6Dingxin Long7Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaHunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, ChinaThis study explores the neuroprotective effects of resveratrol (Resv) against tri-o-cresyl phosphate (TOCP)-induced neurotoxicity in the spinal cord of adult hens. It is well documented that TOCP exposure causes significant neurodegeneration via mechanisms that involve endoplasmic reticulum (ER) stress and impaired autophagy. In this experiment, adult hens were assigned to one of four groups: Control, Resv, TOCP, and TOCP + Resv. The spinal cord tissues were examined through transmission electron microscopy, hematoxylin and eosin (HE) staining, Nissl staining, and Western blotting to evaluate key proteins associated with ER stress and autophagy. Additionally, RT-qPCR and immunofluorescence were employed to measure sirtuin1 (SIRT1) expression. The findings revealed that TOCP induced severe ultrastructural damage, including disrupted myelin sheaths, dilated ER, and extensive neurodegeneration, as confirmed by histological evaluations. The expression levels of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, Beclin-1, P62, and LC3-II were also significantly elevated by TOCP. However, Resv treatment markedly attenuated these pathological changes by reducing ER stress, restoring autophagic flux, and upregulating SIRT1 expression, preserving spinal cord integrity. These results indicate that Resv can effectively counteract TOCP-induced neurotoxicity by modulating ER stress and autophagy, underscoring its potential as a therapeutic agent for neuroprotection.https://www.mdpi.com/2305-6304/12/11/810resveratrolneurotoxicitytri-o-cresyl phosphatesirtuin1endoplasmic reticulum stressautophagy |
| spellingShingle | Xiangsheng Tian Yiquan Ou Shengyuan Shi Qiuhua Zhou Sihong Long Yao Xiang Weichao Zhao Dingxin Long SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic Flux Toxics resveratrol neurotoxicity tri-o-cresyl phosphate sirtuin1 endoplasmic reticulum stress autophagy |
| title | SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic Flux |
| title_full | SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic Flux |
| title_fullStr | SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic Flux |
| title_full_unstemmed | SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic Flux |
| title_short | SIRT1-Dependent Neuroprotection by Resveratrol in TOCP-Induced Spinal Cord Injury: Modulation of ER Stress and Autophagic Flux |
| title_sort | sirt1 dependent neuroprotection by resveratrol in tocp induced spinal cord injury modulation of er stress and autophagic flux |
| topic | resveratrol neurotoxicity tri-o-cresyl phosphate sirtuin1 endoplasmic reticulum stress autophagy |
| url | https://www.mdpi.com/2305-6304/12/11/810 |
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