Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression
Abstract Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant AHN underlying MDD remains unclear. Here we demonstrate that the expression o...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-08-01
|
| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-023-00583-7 |
| _version_ | 1827724709380227072 |
|---|---|
| author | Shao-Qi Zhang Qiao Deng Qi Zhu Zhuang-Li Hu Li-Hong Long Peng-Fei Wu Jin-Gang He Hong-Sheng Chen Zhenyu Yue Jia-Hong Lu Fang Wang Jian-Guo Chen |
| author_facet | Shao-Qi Zhang Qiao Deng Qi Zhu Zhuang-Li Hu Li-Hong Long Peng-Fei Wu Jin-Gang He Hong-Sheng Chen Zhenyu Yue Jia-Hong Lu Fang Wang Jian-Guo Chen |
| author_sort | Shao-Qi Zhang |
| collection | DOAJ |
| description | Abstract Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant AHN underlying MDD remains unclear. Here we demonstrate that the expression of nuclear receptor binding factor 2 (NRBF2), a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, is attenuated in the dentate gyrus (DG) under chronic stress. NRBF2 deficiency inhibits the activity of the VPS34 complex and impairs autophagic flux in adult neural stem cells (aNSCs). Moreover, loss of NRBF2 disrupts the neurogenesis-related protein network and causes exhaustion of aNSC pool, leading to the depression-like phenotype. Strikingly, overexpressing NRBF2 in aNSCs of the DG is sufficient to rescue impaired AHN and depression-like phenotype of mice. Our findings reveal a significant role of NRBF2-dependent autophagy in preventing chronic stress-induced AHN impairment and suggest the therapeutic potential of targeting NRBF2 in MDD treatment. |
| first_indexed | 2024-03-10T22:19:17Z |
| format | Article |
| id | doaj.art-58f02c96d4ad43ee9dd80765316dc3eb |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-03-10T22:19:17Z |
| publishDate | 2023-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-58f02c96d4ad43ee9dd80765316dc3eb2023-11-19T12:20:34ZengNature Publishing GroupCell Discovery2056-59682023-08-019112310.1038/s41421-023-00583-7Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depressionShao-Qi Zhang0Qiao Deng1Qi Zhu2Zhuang-Li Hu3Li-Hong Long4Peng-Fei Wu5Jin-Gang He6Hong-Sheng Chen7Zhenyu Yue8Jia-Hong Lu9Fang Wang10Jian-Guo Chen11Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount SinaiState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant AHN underlying MDD remains unclear. Here we demonstrate that the expression of nuclear receptor binding factor 2 (NRBF2), a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, is attenuated in the dentate gyrus (DG) under chronic stress. NRBF2 deficiency inhibits the activity of the VPS34 complex and impairs autophagic flux in adult neural stem cells (aNSCs). Moreover, loss of NRBF2 disrupts the neurogenesis-related protein network and causes exhaustion of aNSC pool, leading to the depression-like phenotype. Strikingly, overexpressing NRBF2 in aNSCs of the DG is sufficient to rescue impaired AHN and depression-like phenotype of mice. Our findings reveal a significant role of NRBF2-dependent autophagy in preventing chronic stress-induced AHN impairment and suggest the therapeutic potential of targeting NRBF2 in MDD treatment.https://doi.org/10.1038/s41421-023-00583-7 |
| spellingShingle | Shao-Qi Zhang Qiao Deng Qi Zhu Zhuang-Li Hu Li-Hong Long Peng-Fei Wu Jin-Gang He Hong-Sheng Chen Zhenyu Yue Jia-Hong Lu Fang Wang Jian-Guo Chen Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression Cell Discovery |
| title | Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression |
| title_full | Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression |
| title_fullStr | Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression |
| title_full_unstemmed | Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression |
| title_short | Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression |
| title_sort | cell type specific nrbf2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress induced depression |
| url | https://doi.org/10.1038/s41421-023-00583-7 |
| work_keys_str_mv | AT shaoqizhang celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT qiaodeng celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT qizhu celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT zhuanglihu celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT lihonglong celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT pengfeiwu celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT jinganghe celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT hongshengchen celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT zhenyuyue celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT jiahonglu celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT fangwang celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression AT jianguochen celltypespecificnrbf2orchestratesautophagicfluxandadulthippocampalneurogenesisinchronicstressinduceddepression |