Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathy
Introduction:Dysregulation of parvalbumin (PV) interneurons has been implicated in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain poorly understood, and effective treatments are lacking. Given the high energy demands of PV interneurons and the emerging role of mitochond...
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Frontiers Media S.A.
2025-06-01
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| author | Lei Dai Lei Dai Shuxin Gu Shuxin Gu Yibao Zhang Siqi Ma Peishan Wang Peishan Wang Jingyun Zhang Jingyun Zhang Cai Wang Cai Wang Gaowei Su Gaowei Su Qun Fu Wei Zhou Yunxia Fan Yunxia Fan |
| author_facet | Lei Dai Lei Dai Shuxin Gu Shuxin Gu Yibao Zhang Siqi Ma Peishan Wang Peishan Wang Jingyun Zhang Jingyun Zhang Cai Wang Cai Wang Gaowei Su Gaowei Su Qun Fu Wei Zhou Yunxia Fan Yunxia Fan |
| author_sort | Lei Dai |
| collection | DOAJ |
| description | Introduction:Dysregulation of parvalbumin (PV) interneurons has been implicated in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain poorly understood, and effective treatments are lacking. Given the high energy demands of PV interneurons and the emerging role of mitochondrial dynamics in SAE pathophysiology, this study aimed to investigate whether the mitochondrial fission inhibitor Mdivi-1 could alleviate PV interneuron dysfunction and cognitive impairments in a mouse model of SAE.Methods:C57BL/6 male mice were injected with lipopolysaccharide (LPS) to establish an animal model of SAE. Mdivi-1 was administered intraperitoneally 1 h before LPS challenge. Hippocampal tissues were harvested 24 h after LPS challenge for biochemical and histochemical analyses, and mitochondrial morphology was evaluated using transmission electron microscopy. In vivo electrophysiology and behavioral tests were performed between 2 and 4 days after LPS challenge to measure neural oscillations in the hippocampus and assess cognitive function.ResultsOur results showed that LPS induced neuroinflammation, mitochondrial fission abnormalities, ATP depletion, and downregulation of PV interneurons in the hippocampus, collectively contributing to reduced gamma oscillations and cognitive impairments in mice. However, these effects were mitigated by Mdivi-1 treatment.Conclusion:Our study suggests that Mdivi-1 may offer a promising therapeutic approach for attenuating PV interneurons dysfunction and cognitive impairments in SAE. |
| format | Article |
| id | doaj-art-0dd44f2cbec04bdb8352bbe1c91ea1ff |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-0dd44f2cbec04bdb8352bbe1c91ea1ff2025-08-20T02:22:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15250281525028Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathyLei Dai0Lei Dai1Shuxin Gu2Shuxin Gu3Yibao Zhang4Siqi Ma5Peishan Wang6Peishan Wang7Jingyun Zhang8Jingyun Zhang9Cai Wang10Cai Wang11Gaowei Su12Gaowei Su13Qun Fu14Wei Zhou15Yunxia Fan16Yunxia Fan17Department of Anesthesiology, Jintan Affiliated Hospital of Jiangsu University, Changzhou, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Anesthesiology, Jintan Affiliated Hospital of Jiangsu University, Changzhou, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, ChinaDepartment of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, ChinaDepartment of Anesthesiology, Jintan Affiliated Hospital of Jiangsu University, Changzhou, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Anesthesiology, Jintan Affiliated Hospital of Jiangsu University, Changzhou, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Anesthesiology, Jintan Affiliated Hospital of Jiangsu University, Changzhou, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Anesthesiology, Jintan Affiliated Hospital of Jiangsu University, Changzhou, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Anesthesiology, Jintan Affiliated Hospital of Jiangsu University, Changzhou, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaIntroduction:Dysregulation of parvalbumin (PV) interneurons has been implicated in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain poorly understood, and effective treatments are lacking. Given the high energy demands of PV interneurons and the emerging role of mitochondrial dynamics in SAE pathophysiology, this study aimed to investigate whether the mitochondrial fission inhibitor Mdivi-1 could alleviate PV interneuron dysfunction and cognitive impairments in a mouse model of SAE.Methods:C57BL/6 male mice were injected with lipopolysaccharide (LPS) to establish an animal model of SAE. Mdivi-1 was administered intraperitoneally 1 h before LPS challenge. Hippocampal tissues were harvested 24 h after LPS challenge for biochemical and histochemical analyses, and mitochondrial morphology was evaluated using transmission electron microscopy. In vivo electrophysiology and behavioral tests were performed between 2 and 4 days after LPS challenge to measure neural oscillations in the hippocampus and assess cognitive function.ResultsOur results showed that LPS induced neuroinflammation, mitochondrial fission abnormalities, ATP depletion, and downregulation of PV interneurons in the hippocampus, collectively contributing to reduced gamma oscillations and cognitive impairments in mice. However, these effects were mitigated by Mdivi-1 treatment.Conclusion:Our study suggests that Mdivi-1 may offer a promising therapeutic approach for attenuating PV interneurons dysfunction and cognitive impairments in SAE.https://www.frontiersin.org/articles/10.3389/fphar.2025.1525028/fullsepsis-associated encephalopathyMdivi-1parvalbumin interneuronsneuroinflammationcognitive impairment |
| spellingShingle | Lei Dai Lei Dai Shuxin Gu Shuxin Gu Yibao Zhang Siqi Ma Peishan Wang Peishan Wang Jingyun Zhang Jingyun Zhang Cai Wang Cai Wang Gaowei Su Gaowei Su Qun Fu Wei Zhou Yunxia Fan Yunxia Fan Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathy Frontiers in Pharmacology sepsis-associated encephalopathy Mdivi-1 parvalbumin interneurons neuroinflammation cognitive impairment |
| title | Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathy |
| title_full | Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathy |
| title_fullStr | Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathy |
| title_full_unstemmed | Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathy |
| title_short | Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathy |
| title_sort | mitochondrial fission inhibitor mdivi 1 alleviates lipopolysaccharide induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis associated encephalopathy |
| topic | sepsis-associated encephalopathy Mdivi-1 parvalbumin interneurons neuroinflammation cognitive impairment |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1525028/full |
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