Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic process
The dentate gyrus (DG) of the hippocampus regulates stress-related emotional behaviors and ensures neurogenesis throughout life. Neurotrophin-3 (NT-3) is a neurotrophic factor that regulates neuronal differentiation, survival, and synaptic formation in both the peripheral and central nervous systems...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1178555/full |
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| author | Nanami Kasakura Yuka Murata Asuka Shindo Shiho Kitaoka Tomoyuki Furuyashiki Kanzo Suzuki Eri Segi-Nishida |
| author_facet | Nanami Kasakura Yuka Murata Asuka Shindo Shiho Kitaoka Tomoyuki Furuyashiki Kanzo Suzuki Eri Segi-Nishida |
| author_sort | Nanami Kasakura |
| collection | DOAJ |
| description | The dentate gyrus (DG) of the hippocampus regulates stress-related emotional behaviors and ensures neurogenesis throughout life. Neurotrophin-3 (NT-3) is a neurotrophic factor that regulates neuronal differentiation, survival, and synaptic formation in both the peripheral and central nervous systems. NT-3 is expressed in the adult DG of the hippocampus; several chronic stress conditions enhance NT-3 expression in rodents. However, functional modulation of the adult DG by NT-3 signaling remains unclear. To directly investigate the impact of NT-3 on DG function, NT-3 was overexpressed in the hippocampal ventral DG by an adeno-associated virus carrying NT-3 (AAV-NT-3). Four weeks following the AAV-NT-3 injection, high NT-3 expression was observed in the ventral DG. We examined the influence of NT-3 overexpression on the neuronal responses and neurogenic processes in the ventral DG. NT-3 overexpression significantly increased the expression of the mature DG neuronal marker calbindin and immediate early genes, such as Fos and Fosb, thereby suggesting DG neuronal activation. During neurogenesis, the number of proliferating cells and immature neurons in the subgranular zone of the DG significantly decreased in the AAV-NT-3 group. Among the neurogenesis-related factors, Vegfd, Lgr6, Bmp7, and Drd1 expression significantly decreased. These results demonstrated that high NT-3 levels in the hippocampus regulate the activation of mature DG neurons and suppress the early phase of neurogenic processes, suggesting a possible role of NT-3 in the regulation of adult hippocampal function under stress conditions. |
| first_indexed | 2024-03-12T21:32:43Z |
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| id | doaj.art-9a07f3aefdba4a008a9d84e68eaddb7e |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-12T21:32:43Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-9a07f3aefdba4a008a9d84e68eaddb7e2023-07-27T16:44:44ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-07-011710.3389/fnins.2023.11785551178555Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic processNanami Kasakura0Yuka Murata1Asuka Shindo2Shiho Kitaoka3Tomoyuki Furuyashiki4Kanzo Suzuki5Eri Segi-Nishida6Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, JapanDepartment of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, JapanDepartment of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, JapanDepartment of Pharmacology, School of Medicine, Hyogo Medical University, Hyogo, JapanDivision of Pharmacology, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, JapanDepartment of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, JapanThe dentate gyrus (DG) of the hippocampus regulates stress-related emotional behaviors and ensures neurogenesis throughout life. Neurotrophin-3 (NT-3) is a neurotrophic factor that regulates neuronal differentiation, survival, and synaptic formation in both the peripheral and central nervous systems. NT-3 is expressed in the adult DG of the hippocampus; several chronic stress conditions enhance NT-3 expression in rodents. However, functional modulation of the adult DG by NT-3 signaling remains unclear. To directly investigate the impact of NT-3 on DG function, NT-3 was overexpressed in the hippocampal ventral DG by an adeno-associated virus carrying NT-3 (AAV-NT-3). Four weeks following the AAV-NT-3 injection, high NT-3 expression was observed in the ventral DG. We examined the influence of NT-3 overexpression on the neuronal responses and neurogenic processes in the ventral DG. NT-3 overexpression significantly increased the expression of the mature DG neuronal marker calbindin and immediate early genes, such as Fos and Fosb, thereby suggesting DG neuronal activation. During neurogenesis, the number of proliferating cells and immature neurons in the subgranular zone of the DG significantly decreased in the AAV-NT-3 group. Among the neurogenesis-related factors, Vegfd, Lgr6, Bmp7, and Drd1 expression significantly decreased. These results demonstrated that high NT-3 levels in the hippocampus regulate the activation of mature DG neurons and suppress the early phase of neurogenic processes, suggesting a possible role of NT-3 in the regulation of adult hippocampal function under stress conditions.https://www.frontiersin.org/articles/10.3389/fnins.2023.1178555/fullNT-3hippocampusneurogenesisdentate gyrusmaturationAAV |
| spellingShingle | Nanami Kasakura Yuka Murata Asuka Shindo Shiho Kitaoka Tomoyuki Furuyashiki Kanzo Suzuki Eri Segi-Nishida Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic process Frontiers in Neuroscience NT-3 hippocampus neurogenesis dentate gyrus maturation AAV |
| title | Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic process |
| title_full | Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic process |
| title_fullStr | Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic process |
| title_full_unstemmed | Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic process |
| title_short | Overexpression of NT-3 in the hippocampus suppresses the early phase of the adult neurogenic process |
| title_sort | overexpression of nt 3 in the hippocampus suppresses the early phase of the adult neurogenic process |
| topic | NT-3 hippocampus neurogenesis dentate gyrus maturation AAV |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1178555/full |
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