Role of endogenous NT-3 in neuronal activity and neurogenesis in the hippocampal dentate gyrus

Neurotrophin-3 (NT-3) is a neurotrophic factor that regulates neuronal differentiation and synaptic plasticity. In the adult central nervous system, NT-3 is predominantly expressed in the hippocampal dentate gyrus (DG). Chronic antidepressant treatment suppresses Ntf3 expression in the DG; however,...

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Main Authors: Nanami Kasakura, Yuka Murata, Kanzo Suzuki, Eri Segi-Nishida
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Neuroscience Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0168010225001063
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author Nanami Kasakura
Yuka Murata
Kanzo Suzuki
Eri Segi-Nishida
author_facet Nanami Kasakura
Yuka Murata
Kanzo Suzuki
Eri Segi-Nishida
author_sort Nanami Kasakura
collection DOAJ
description Neurotrophin-3 (NT-3) is a neurotrophic factor that regulates neuronal differentiation and synaptic plasticity. In the adult central nervous system, NT-3 is predominantly expressed in the hippocampal dentate gyrus (DG). Chronic antidepressant treatment suppresses Ntf3 expression in the DG; however, its functional significance remains unclear. To investigate the role of NT-3 in the adult DG, an adeno-associated virus (AAV)-mediated knockdown system was employed in mice. Immunohistochemical analysis revealed that TrkC, the high-affinity receptor for NT-3, was highly expressed in the DG. Under basal conditions, NT-3 knockdown significantly reduced the expression of FosB, an activity-dependent marker. Gene expression analysis showed that Arc, Egr1, and Fosb expressions were also significantly decreased. Although NT-3 knockdown did not affect cell proliferation in the DG, it impaired dendritic elongation in immature neurons. Additionally, NT-3 knockdown significantly reduced Npy expression. These findings suggest that endogenous NT-3 in the adult DG regulates both basal neuronal activity and newborn neuronal differentiation, contributing to hippocampal homeostasis. Further research is required to determine whether NT-3 downregulation induced by chronic antidepressant treatment influences neuronal activity and hippocampal plasticity in neuropsychiatric conditions.
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spelling doaj-art-0a9ef07fe8b6447ca97e3736e16989392025-08-20T03:41:57ZengElsevierNeuroscience Research0168-01022025-09-0121810492310.1016/j.neures.2025.104923Role of endogenous NT-3 in neuronal activity and neurogenesis in the hippocampal dentate gyrusNanami Kasakura0Yuka Murata1Kanzo Suzuki2Eri Segi-Nishida3Department 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, JapanCorrespondence to: 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.; Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, JapanNeurotrophin-3 (NT-3) is a neurotrophic factor that regulates neuronal differentiation and synaptic plasticity. In the adult central nervous system, NT-3 is predominantly expressed in the hippocampal dentate gyrus (DG). Chronic antidepressant treatment suppresses Ntf3 expression in the DG; however, its functional significance remains unclear. To investigate the role of NT-3 in the adult DG, an adeno-associated virus (AAV)-mediated knockdown system was employed in mice. Immunohistochemical analysis revealed that TrkC, the high-affinity receptor for NT-3, was highly expressed in the DG. Under basal conditions, NT-3 knockdown significantly reduced the expression of FosB, an activity-dependent marker. Gene expression analysis showed that Arc, Egr1, and Fosb expressions were also significantly decreased. Although NT-3 knockdown did not affect cell proliferation in the DG, it impaired dendritic elongation in immature neurons. Additionally, NT-3 knockdown significantly reduced Npy expression. These findings suggest that endogenous NT-3 in the adult DG regulates both basal neuronal activity and newborn neuronal differentiation, contributing to hippocampal homeostasis. Further research is required to determine whether NT-3 downregulation induced by chronic antidepressant treatment influences neuronal activity and hippocampal plasticity in neuropsychiatric conditions.http://www.sciencedirect.com/science/article/pii/S0168010225001063NT-3HippocampusDentate gyrusKnockdownNeurogenesisImmediate-early genes
spellingShingle Nanami Kasakura
Yuka Murata
Kanzo Suzuki
Eri Segi-Nishida
Role of endogenous NT-3 in neuronal activity and neurogenesis in the hippocampal dentate gyrus
Neuroscience Research
NT-3
Hippocampus
Dentate gyrus
Knockdown
Neurogenesis
Immediate-early genes
title Role of endogenous NT-3 in neuronal activity and neurogenesis in the hippocampal dentate gyrus
title_full Role of endogenous NT-3 in neuronal activity and neurogenesis in the hippocampal dentate gyrus
title_fullStr Role of endogenous NT-3 in neuronal activity and neurogenesis in the hippocampal dentate gyrus
title_full_unstemmed Role of endogenous NT-3 in neuronal activity and neurogenesis in the hippocampal dentate gyrus
title_short Role of endogenous NT-3 in neuronal activity and neurogenesis in the hippocampal dentate gyrus
title_sort role of endogenous nt 3 in neuronal activity and neurogenesis in the hippocampal dentate gyrus
topic NT-3
Hippocampus
Dentate gyrus
Knockdown
Neurogenesis
Immediate-early genes
url http://www.sciencedirect.com/science/article/pii/S0168010225001063
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AT kanzosuzuki roleofendogenousnt3inneuronalactivityandneurogenesisinthehippocampaldentategyrus
AT eriseginishida roleofendogenousnt3inneuronalactivityandneurogenesisinthehippocampaldentategyrus