Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders
IntroductionAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and communication, along with restricted and repetitive behaviors. Both genetic and environmental factors contribute to ASD, with prenatal exposure to valproic acid (VPA) and...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Neural Circuits |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncir.2024.1504191/full |
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| author | Lihao Sun Nobuhiko Ohashi Takuma Mori Takuma Mori Yuka Mizuno Weichen Zang Qi Guo Emi Kouyama-Suzuki Yoshinori Shirai Katsuhiko Tabuchi Katsuhiko Tabuchi |
| author_facet | Lihao Sun Nobuhiko Ohashi Takuma Mori Takuma Mori Yuka Mizuno Weichen Zang Qi Guo Emi Kouyama-Suzuki Yoshinori Shirai Katsuhiko Tabuchi Katsuhiko Tabuchi |
| author_sort | Lihao Sun |
| collection | DOAJ |
| description | IntroductionAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and communication, along with restricted and repetitive behaviors. Both genetic and environmental factors contribute to ASD, with prenatal exposure to valproic acid (VPA) and nicotine being linked to increased risk. Impaired adult hippocampal neurogenesis, particularly in the ventral region, is thought to play a role in the social deficits observed in ASD.MethodsIn this study, we investigated social behavior and adult hippocampal neurogenesis in C57BL/6J mice prenatally exposed to VPA or nicotine, as well as in genetically modified ASD models, including IQSEC2 knockout (KO) and NLGN3-R451C knock-in (KI) mice. Sociability and social novelty preference were evaluated using a three-chamber social interaction test. Adult hippocampal neurogenesis was assessed by BrdU and DCX immunofluorescence to identify newborn and immature neurons.ResultsVPA-exposed mice displayed significant deficits in social interaction, while nicotine-exposed mice exhibited mild impairment in social novelty preference. Both IQSEC2 KO and NLGN3-R451C KI mice demonstrated reduced adult neurogenesis, particularly in the ventral hippocampus, a region associated with social behavior and emotion. Across all ASD mouse models, a significant reduction in BrdU+/NeuN+ cells in the ventral hippocampus was observed, while dorsal hippocampal neurogenesis remained relatively unaffected. Similar reductions in DCX-positive cells were identified in VPA, nicotine, and NLGN3-R451C KI mice, indicating impaired proliferation or differentiation of neuronal progenitors.DiscussionThese findings suggest that impaired adult neurogenesis in the ventral hippocampus is a common hallmark across ASD mouse models and may underlie social behavior deficits. This study provides insight into region-specific neurogenic alterations linked to ASD pathophysiology and highlights potential targets for therapeutic interventions. |
| format | Article |
| id | doaj-art-cb0e37b5f02e4aa2bc5f238734ef6f98 |
| institution | DOAJ |
| issn | 1662-5110 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neural Circuits |
| spelling | doaj-art-cb0e37b5f02e4aa2bc5f238734ef6f982025-08-20T02:40:24ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102024-12-011810.3389/fncir.2024.15041911504191Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disordersLihao Sun0Nobuhiko Ohashi1Takuma Mori2Takuma Mori3Yuka Mizuno4Weichen Zang5Qi Guo6Emi Kouyama-Suzuki7Yoshinori Shirai8Katsuhiko Tabuchi9Katsuhiko Tabuchi10Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Neuroinnovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, JapanDepartment of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Neuroinnovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, JapanIntroductionAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and communication, along with restricted and repetitive behaviors. Both genetic and environmental factors contribute to ASD, with prenatal exposure to valproic acid (VPA) and nicotine being linked to increased risk. Impaired adult hippocampal neurogenesis, particularly in the ventral region, is thought to play a role in the social deficits observed in ASD.MethodsIn this study, we investigated social behavior and adult hippocampal neurogenesis in C57BL/6J mice prenatally exposed to VPA or nicotine, as well as in genetically modified ASD models, including IQSEC2 knockout (KO) and NLGN3-R451C knock-in (KI) mice. Sociability and social novelty preference were evaluated using a three-chamber social interaction test. Adult hippocampal neurogenesis was assessed by BrdU and DCX immunofluorescence to identify newborn and immature neurons.ResultsVPA-exposed mice displayed significant deficits in social interaction, while nicotine-exposed mice exhibited mild impairment in social novelty preference. Both IQSEC2 KO and NLGN3-R451C KI mice demonstrated reduced adult neurogenesis, particularly in the ventral hippocampus, a region associated with social behavior and emotion. Across all ASD mouse models, a significant reduction in BrdU+/NeuN+ cells in the ventral hippocampus was observed, while dorsal hippocampal neurogenesis remained relatively unaffected. Similar reductions in DCX-positive cells were identified in VPA, nicotine, and NLGN3-R451C KI mice, indicating impaired proliferation or differentiation of neuronal progenitors.DiscussionThese findings suggest that impaired adult neurogenesis in the ventral hippocampus is a common hallmark across ASD mouse models and may underlie social behavior deficits. This study provides insight into region-specific neurogenic alterations linked to ASD pathophysiology and highlights potential targets for therapeutic interventions.https://www.frontiersin.org/articles/10.3389/fncir.2024.1504191/fulladult hippocampal neurogenesisprenatal nicotine exposurevalproic acidIQSEC2neuroligin 3autism spectrum disorder |
| spellingShingle | Lihao Sun Nobuhiko Ohashi Takuma Mori Takuma Mori Yuka Mizuno Weichen Zang Qi Guo Emi Kouyama-Suzuki Yoshinori Shirai Katsuhiko Tabuchi Katsuhiko Tabuchi Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders Frontiers in Neural Circuits adult hippocampal neurogenesis prenatal nicotine exposure valproic acid IQSEC2 neuroligin 3 autism spectrum disorder |
| title | Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders |
| title_full | Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders |
| title_fullStr | Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders |
| title_full_unstemmed | Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders |
| title_short | Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders |
| title_sort | adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders |
| topic | adult hippocampal neurogenesis prenatal nicotine exposure valproic acid IQSEC2 neuroligin 3 autism spectrum disorder |
| url | https://www.frontiersin.org/articles/10.3389/fncir.2024.1504191/full |
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