Astrocytic AEG-1 drives neuroinflammation and enhances seizure susceptibility
Astrocyte-elevated gene-1 (AEG-1), also known as metadherin (MTDH) has emerged as a potent oncogene expressed in cancers. An increasing body of evidence indicates AEG-1 plays a pivotal role in various brain pathophysiological processes. Abnormal expression of AEG-1 in astrocytes has been correlated...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125001731 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849327788907036672 |
|---|---|
| author | Yuzhou Chen Yunbo Yu Jinhao Kou Honggang Qi Canyu Zhang Feiyu Wang Lijie Zhou Xuemei Liang Kang Xu Cong Zhang Aifeng Zhang Xiufang Liu Chenchen Zhang Guangming Gan Jie Sun Xinjian Zhu |
| author_facet | Yuzhou Chen Yunbo Yu Jinhao Kou Honggang Qi Canyu Zhang Feiyu Wang Lijie Zhou Xuemei Liang Kang Xu Cong Zhang Aifeng Zhang Xiufang Liu Chenchen Zhang Guangming Gan Jie Sun Xinjian Zhu |
| author_sort | Yuzhou Chen |
| collection | DOAJ |
| description | Astrocyte-elevated gene-1 (AEG-1), also known as metadherin (MTDH) has emerged as a potent oncogene expressed in cancers. An increasing body of evidence indicates AEG-1 plays a pivotal role in various brain pathophysiological processes. Abnormal expression of AEG-1 in astrocytes has been correlated with inflammatory response, suggesting a possible role of AEG-1 in the pathogenesis of inflammatory encephalopathy. Here, we analyzed single-cell RNA sequencing data to explore the heterogeneity of astrocyte subpopulations in a mouse model induced by lipopolysaccharide (LPS), and investigated the effect of astrocytic AEG-1 on lipopolysaccharide (LPS)-induced inflammatory response and seizure susceptibility in mice, as well as in an in vitro astrocyte culture model. Our single-cell RNA sequencing analysis reveals that AEG-1-expressing astrocyte subpopulation is associated with inflammatory responses. LPS-induced inflammatory response is accompanied by increased AEG-1 expression in astrocytes. Depletion of astrocytic AEG-1, however, suppressed LPS-induced neuroinflammation and high seizure susceptibility both in vivo and in vitro. Furthermore, we find that AEG-1 induces neuroinflammatory cytokine expression and enhances seizure susceptibility, which is dependent on NF-κB signaling pathway. These data identify an important role of astrocytic AEG-1 in LPS-induced neuroinflammation and high seizure susceptibility, demonstrating that AEG-1 mediates downstream neuroinflammatory and epileptic effect via NF-κB signaling pathway. |
| format | Article |
| id | doaj-art-e4ac32a3ed284e58a3c819629ad78018 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-e4ac32a3ed284e58a3c819629ad780182025-08-20T03:47:45ZengElsevierNeurobiology of Disease1095-953X2025-08-0121210695710.1016/j.nbd.2025.106957Astrocytic AEG-1 drives neuroinflammation and enhances seizure susceptibilityYuzhou Chen0Yunbo Yu1Jinhao Kou2Honggang Qi3Canyu Zhang4Feiyu Wang5Lijie Zhou6Xuemei Liang7Kang Xu8Cong Zhang9Aifeng Zhang10Xiufang Liu11Chenchen Zhang12Guangming Gan13Jie Sun14Xinjian Zhu15Department of Pharmacology, Medical School of Southeast University, Nanjing, China; Department of Anesthesiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pathology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pathogenic Biology and Immunology, Medical School of Southeast University, Nanjing, ChinaTransmission Electron Microscopy Center, Medical School of Southeast University, Nanjing, ChinaTransmission Electron Microscopy Center, Medical School of Southeast University, Nanjing, China; Department of Genetics and Developmental Biology, Medical School of Southeast University, Nanjing, ChinaDepartment of Anesthesiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China; Correspondence to: J Sun, Department of Anesthesiology, Zhongda Hospital, Medical School of Southeast University, 210009 Nanjing, Jiangsu, China.Department of Pharmacology, Medical School of Southeast University, Nanjing, China; Epilepsy Center at Zhongda Hospital, Medical School of Southeast University, Nanjing, China; Correspondence to: X Zhu, Department of Pharmacology, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing, China.Astrocyte-elevated gene-1 (AEG-1), also known as metadherin (MTDH) has emerged as a potent oncogene expressed in cancers. An increasing body of evidence indicates AEG-1 plays a pivotal role in various brain pathophysiological processes. Abnormal expression of AEG-1 in astrocytes has been correlated with inflammatory response, suggesting a possible role of AEG-1 in the pathogenesis of inflammatory encephalopathy. Here, we analyzed single-cell RNA sequencing data to explore the heterogeneity of astrocyte subpopulations in a mouse model induced by lipopolysaccharide (LPS), and investigated the effect of astrocytic AEG-1 on lipopolysaccharide (LPS)-induced inflammatory response and seizure susceptibility in mice, as well as in an in vitro astrocyte culture model. Our single-cell RNA sequencing analysis reveals that AEG-1-expressing astrocyte subpopulation is associated with inflammatory responses. LPS-induced inflammatory response is accompanied by increased AEG-1 expression in astrocytes. Depletion of astrocytic AEG-1, however, suppressed LPS-induced neuroinflammation and high seizure susceptibility both in vivo and in vitro. Furthermore, we find that AEG-1 induces neuroinflammatory cytokine expression and enhances seizure susceptibility, which is dependent on NF-κB signaling pathway. These data identify an important role of astrocytic AEG-1 in LPS-induced neuroinflammation and high seizure susceptibility, demonstrating that AEG-1 mediates downstream neuroinflammatory and epileptic effect via NF-κB signaling pathway.http://www.sciencedirect.com/science/article/pii/S0969996125001731AstrocyteAEG-1LPSNeuroinflammationSeizure |
| spellingShingle | Yuzhou Chen Yunbo Yu Jinhao Kou Honggang Qi Canyu Zhang Feiyu Wang Lijie Zhou Xuemei Liang Kang Xu Cong Zhang Aifeng Zhang Xiufang Liu Chenchen Zhang Guangming Gan Jie Sun Xinjian Zhu Astrocytic AEG-1 drives neuroinflammation and enhances seizure susceptibility Neurobiology of Disease Astrocyte AEG-1 LPS Neuroinflammation Seizure |
| title | Astrocytic AEG-1 drives neuroinflammation and enhances seizure susceptibility |
| title_full | Astrocytic AEG-1 drives neuroinflammation and enhances seizure susceptibility |
| title_fullStr | Astrocytic AEG-1 drives neuroinflammation and enhances seizure susceptibility |
| title_full_unstemmed | Astrocytic AEG-1 drives neuroinflammation and enhances seizure susceptibility |
| title_short | Astrocytic AEG-1 drives neuroinflammation and enhances seizure susceptibility |
| title_sort | astrocytic aeg 1 drives neuroinflammation and enhances seizure susceptibility |
| topic | Astrocyte AEG-1 LPS Neuroinflammation Seizure |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125001731 |
| work_keys_str_mv | AT yuzhouchen astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT yunboyu astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT jinhaokou astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT honggangqi astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT canyuzhang astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT feiyuwang astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT lijiezhou astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT xuemeiliang astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT kangxu astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT congzhang astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT aifengzhang astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT xiufangliu astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT chenchenzhang astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT guangminggan astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT jiesun astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility AT xinjianzhu astrocyticaeg1drivesneuroinflammationandenhancesseizuresusceptibility |