Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice
The hippocampus plays an important role in maintaining normal cognitive function and is closely associated with the neuropathogenesis of dementia. Wnt signaling is relevant to neuronal development and maturation, synaptic formation, and plasticity. The role of Wnt10a in hippocampus-associated cognit...
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MDPI AG
2022-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/7/1500 |
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| author | Jia-He Zhang Takashi Tasaki Manabu Tsukamoto Ke-Yong Wang Kin-ya Kubo Kagaku Azuma |
| author_facet | Jia-He Zhang Takashi Tasaki Manabu Tsukamoto Ke-Yong Wang Kin-ya Kubo Kagaku Azuma |
| author_sort | Jia-He Zhang |
| collection | DOAJ |
| description | The hippocampus plays an important role in maintaining normal cognitive function and is closely associated with the neuropathogenesis of dementia. Wnt signaling is relevant to neuronal development and maturation, synaptic formation, and plasticity. The role of Wnt10a in hippocampus-associated cognition, however, is largely unclear. Here, we examined the morphological and functional alterations in the hippocampus of Wnt10a-knockout (Wnt10a<sup>-/-</sup>) mice. Neurobehavioral tests revealed that Wnt10a<sup>-/-</sup> mice exhibited spatial memory impairment and anxiety-like behavior. Immunostaining and Western blot findings showed that the protein expressions of β-catenin, brain-derived neurotrophic factor, and doublecortin were significantly decreased and that the number of activated microglia increased, accompanied by amyloid-β accumulation, synaptic dysfunction, and microglia-associated neuroinflammation in the hippocampi of Wnt10a<sup>-/-</sup> mice. Our findings revealed that the deletion of Wnt10a decreased neurogenesis, impaired synaptic function, and induced hippocampal neuroinflammation, eventually leading to hippocampal neurodegeneration and memory deficit, possibly through the β-catenin signaling pathway, providing a novel insight into preventive approaches for hippocampus-dependent cognitive impairment. |
| first_indexed | 2024-03-09T03:40:10Z |
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| id | doaj.art-37a17da8c4534135a1d5d0ed194521ba |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T03:40:10Z |
| publishDate | 2022-06-01 |
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| series | Biomedicines |
| spelling | doaj.art-37a17da8c4534135a1d5d0ed194521ba2023-12-03T14:41:08ZengMDPI AGBiomedicines2227-90592022-06-01107150010.3390/biomedicines10071500Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in MiceJia-He Zhang0Takashi Tasaki1Manabu Tsukamoto2Ke-Yong Wang3Kin-ya Kubo4Kagaku Azuma5Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyusyu 807-8555, Fukuoka, JapanDepartment of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Kanagawa, JapanDepartment of Orthopedic Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyusyu 807-8555, Fukuoka, JapanShared-Use Research Center, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyusyu 807-8555, Fukuoka, JapanFaculty of Human Life and Environmental Science, Nagoya Women’s University, 3-40 Shioji-cho, Mizuho-ku, Nagoya 467-8610, Aichi, JapanDepartment of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyusyu 807-8555, Fukuoka, JapanThe hippocampus plays an important role in maintaining normal cognitive function and is closely associated with the neuropathogenesis of dementia. Wnt signaling is relevant to neuronal development and maturation, synaptic formation, and plasticity. The role of Wnt10a in hippocampus-associated cognition, however, is largely unclear. Here, we examined the morphological and functional alterations in the hippocampus of Wnt10a-knockout (Wnt10a<sup>-/-</sup>) mice. Neurobehavioral tests revealed that Wnt10a<sup>-/-</sup> mice exhibited spatial memory impairment and anxiety-like behavior. Immunostaining and Western blot findings showed that the protein expressions of β-catenin, brain-derived neurotrophic factor, and doublecortin were significantly decreased and that the number of activated microglia increased, accompanied by amyloid-β accumulation, synaptic dysfunction, and microglia-associated neuroinflammation in the hippocampi of Wnt10a<sup>-/-</sup> mice. Our findings revealed that the deletion of Wnt10a decreased neurogenesis, impaired synaptic function, and induced hippocampal neuroinflammation, eventually leading to hippocampal neurodegeneration and memory deficit, possibly through the β-catenin signaling pathway, providing a novel insight into preventive approaches for hippocampus-dependent cognitive impairment.https://www.mdpi.com/2227-9059/10/7/1500hippocampusWnt10aneurogenesisneuroinflammationspatial memorysynapse |
| spellingShingle | Jia-He Zhang Takashi Tasaki Manabu Tsukamoto Ke-Yong Wang Kin-ya Kubo Kagaku Azuma Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice Biomedicines hippocampus Wnt10a neurogenesis neuroinflammation spatial memory synapse |
| title | Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice |
| title_full | Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice |
| title_fullStr | Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice |
| title_full_unstemmed | Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice |
| title_short | Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice |
| title_sort | deletion of wnt10a is implicated in hippocampal neurodegeneration in mice |
| topic | hippocampus Wnt10a neurogenesis neuroinflammation spatial memory synapse |
| url | https://www.mdpi.com/2227-9059/10/7/1500 |
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