Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fission

Neurogenesis is a fundamental process in the development and plasticity of the nervous system, and its regulation is tightly linked to mitochondrial dynamics. Imbalanced mitochondrial dynamics can result in oxidative stress, which has been implicated in various neurological disorders. Paraquat (PQ),...

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Main Authors: Bing Zhang, Yuwei Zhang, Zhenzi Zuo, Guiya Xiong, Huan Luo, Bo Song, Lina Zhao, Zhijun Zhou, Xiuli Chang
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651323004438
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author Bing Zhang
Yuwei Zhang
Zhenzi Zuo
Guiya Xiong
Huan Luo
Bo Song
Lina Zhao
Zhijun Zhou
Xiuli Chang
author_facet Bing Zhang
Yuwei Zhang
Zhenzi Zuo
Guiya Xiong
Huan Luo
Bo Song
Lina Zhao
Zhijun Zhou
Xiuli Chang
author_sort Bing Zhang
collection DOAJ
description Neurogenesis is a fundamental process in the development and plasticity of the nervous system, and its regulation is tightly linked to mitochondrial dynamics. Imbalanced mitochondrial dynamics can result in oxidative stress, which has been implicated in various neurological disorders. Paraquat (PQ), a commonly used agricultural chemical known to be neurotoxic, induces oxidative stress that can lead to mitochondrial fragmentation. In this study, we investigated the effects of PQ on neurogenesis in primary murine neural progenitor cells (mNPCs) isolated from neonatal C57BL/6 mice. We treated the mNPCs with 0–40 μM PQ for 24 h and observed that PQ inhibited their proliferation, migration, and differentiation into neurons in a concentration-dependent manner. Moreover, PQ induced excessive mitochondrial fragmentation and upregulated the expression of Drp-1, p-Drp1, and Fis-1, while downregulating the expression of Mfn2 and Opa1. To confirm our findings, we used Mdivi-1, an inhibitor of mitochondrial fission, which reversed the adverse effects of PQ on neurogenesis, particularly differentiation into neurons and migration of mNPCs. Additionally, we found that Mito-TEMPO, a mitochondria-targeted antioxidant, ameliorated excessive mitochondrial fragmentation caused by PQ. Our study suggests that PQ exposure impairs neurogenesis by inducing excessive mitochondrial fission and abnormal mitochondrial fragmentation via oxidative stress. These findings identify mitochondrial fission as a potential therapeutic target for PQ-induced neurotoxicity. Further research is needed to elucidate the underlying mechanisms of mitochondrial dynamics and neurogenesis in the context of oxidative stress-induced neurological disorders.
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spelling doaj.art-bdca95539a78415fa52d80d01d0bdd942023-05-05T04:39:43ZengElsevierEcotoxicology and Environmental Safety0147-65132023-06-01257114939Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fissionBing Zhang0Yuwei Zhang1Zhenzi Zuo2Guiya Xiong3Huan Luo4Bo Song5Lina Zhao6Zhijun Zhou7Xiuli Chang8School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaSchool of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaSchool of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaSchool of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaSchool of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaSchool of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaSchool of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaSchool of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaCorresponding author.; School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, ChinaNeurogenesis is a fundamental process in the development and plasticity of the nervous system, and its regulation is tightly linked to mitochondrial dynamics. Imbalanced mitochondrial dynamics can result in oxidative stress, which has been implicated in various neurological disorders. Paraquat (PQ), a commonly used agricultural chemical known to be neurotoxic, induces oxidative stress that can lead to mitochondrial fragmentation. In this study, we investigated the effects of PQ on neurogenesis in primary murine neural progenitor cells (mNPCs) isolated from neonatal C57BL/6 mice. We treated the mNPCs with 0–40 μM PQ for 24 h and observed that PQ inhibited their proliferation, migration, and differentiation into neurons in a concentration-dependent manner. Moreover, PQ induced excessive mitochondrial fragmentation and upregulated the expression of Drp-1, p-Drp1, and Fis-1, while downregulating the expression of Mfn2 and Opa1. To confirm our findings, we used Mdivi-1, an inhibitor of mitochondrial fission, which reversed the adverse effects of PQ on neurogenesis, particularly differentiation into neurons and migration of mNPCs. Additionally, we found that Mito-TEMPO, a mitochondria-targeted antioxidant, ameliorated excessive mitochondrial fragmentation caused by PQ. Our study suggests that PQ exposure impairs neurogenesis by inducing excessive mitochondrial fission and abnormal mitochondrial fragmentation via oxidative stress. These findings identify mitochondrial fission as a potential therapeutic target for PQ-induced neurotoxicity. Further research is needed to elucidate the underlying mechanisms of mitochondrial dynamics and neurogenesis in the context of oxidative stress-induced neurological disorders.http://www.sciencedirect.com/science/article/pii/S0147651323004438ParaquatNeurogenesisMitochondrial fragmentationDrp1
spellingShingle Bing Zhang
Yuwei Zhang
Zhenzi Zuo
Guiya Xiong
Huan Luo
Bo Song
Lina Zhao
Zhijun Zhou
Xiuli Chang
Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fission
Ecotoxicology and Environmental Safety
Paraquat
Neurogenesis
Mitochondrial fragmentation
Drp1
title Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fission
title_full Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fission
title_fullStr Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fission
title_full_unstemmed Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fission
title_short Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fission
title_sort paraquat induced neurogenesis abnormalities via drp1 mediated mitochondrial fission
topic Paraquat
Neurogenesis
Mitochondrial fragmentation
Drp1
url http://www.sciencedirect.com/science/article/pii/S0147651323004438
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