Effects of early tooth loss on chronic stress and progression of neuropathogenesis of Alzheimer’s disease in adult Alzheimer’s model AppNL-G-F mice
IntroductionAlzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by accumulated amyloid-β (Aβ) plaques, aggregated phosphorylated tau protein, gliosis-associated neuroinflammation, synaptic dysfunction, and cognitive impairment. Many cohort studies indicate that toot...
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| Format: | Article |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1361847/full |
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| author | Suzuko Ochi Kumiko Yamada Takashi Saito Takaomi C. Saido Mitsuo Iinuma Kagaku Azuma Kin-Ya Kubo |
| author_facet | Suzuko Ochi Kumiko Yamada Takashi Saito Takaomi C. Saido Mitsuo Iinuma Kagaku Azuma Kin-Ya Kubo |
| author_sort | Suzuko Ochi |
| collection | DOAJ |
| description | IntroductionAlzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by accumulated amyloid-β (Aβ) plaques, aggregated phosphorylated tau protein, gliosis-associated neuroinflammation, synaptic dysfunction, and cognitive impairment. Many cohort studies indicate that tooth loss is a risk factor for AD. The detailed mechanisms underlying the association between AD and tooth loss, however, are not yet fully understood.MethodsWe explored the involvement of early tooth loss in the neuropathogenesis of the adult AppNL-G-F mouse AD model. The maxillary molars were extracted bilaterally in 1-month-old male mice soon after tooth eruption.ResultsPlasma corticosterone levels were increased and spatial learning memory was impaired in these mice at 6 months of age. The cerebral cortex and hippocampus of AD mice with extracted teeth showed an increased accumulation of Aβ plaques and phosphorylated tau proteins, and increased secretion of the proinflammatory cytokines, including interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α), accompanied by an increased number of microglia and astrocytes, and decreased synaptophysin expression. AD mice with extracted teeth also had a shorter lifespan than the control mice.DiscussionThese findings revealed that long-term tooth loss is a chronic stressor, activating the recruitment of microglia and astrocytes; exacerbating neuroinflammation, Aβ deposition, phosphorylated tau accumulation, and synaptic dysfunction; and leading to spatial learning and memory impairments in AD model mice. |
| first_indexed | 2024-03-07T21:43:29Z |
| format | Article |
| id | doaj.art-5fcf8d1ccf79443b89280e07717274de |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-07T21:43:29Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-5fcf8d1ccf79443b89280e07717274de2024-02-26T04:34:27ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652024-02-011610.3389/fnagi.2024.13618471361847Effects of early tooth loss on chronic stress and progression of neuropathogenesis of Alzheimer’s disease in adult Alzheimer’s model AppNL-G-F miceSuzuko Ochi0Kumiko Yamada1Takashi Saito2Takaomi C. Saido3Mitsuo Iinuma4Kagaku Azuma5Kin-Ya Kubo6Department of Pediatric Dentistry, Asahi University School of Dentistry, Mizuho, JapanDepartment of Health and Nutrition, Faculty of Health Science, Nagoya Women’s University, Nagoya, JapanDepartment of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako, JapanDepartment of Pediatric Dentistry, Asahi University School of Dentistry, Mizuho, JapanDepartment of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, JapanGraduate School of Human Life Science, Nagoya Women’s University, Nagoya, JapanIntroductionAlzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by accumulated amyloid-β (Aβ) plaques, aggregated phosphorylated tau protein, gliosis-associated neuroinflammation, synaptic dysfunction, and cognitive impairment. Many cohort studies indicate that tooth loss is a risk factor for AD. The detailed mechanisms underlying the association between AD and tooth loss, however, are not yet fully understood.MethodsWe explored the involvement of early tooth loss in the neuropathogenesis of the adult AppNL-G-F mouse AD model. The maxillary molars were extracted bilaterally in 1-month-old male mice soon after tooth eruption.ResultsPlasma corticosterone levels were increased and spatial learning memory was impaired in these mice at 6 months of age. The cerebral cortex and hippocampus of AD mice with extracted teeth showed an increased accumulation of Aβ plaques and phosphorylated tau proteins, and increased secretion of the proinflammatory cytokines, including interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α), accompanied by an increased number of microglia and astrocytes, and decreased synaptophysin expression. AD mice with extracted teeth also had a shorter lifespan than the control mice.DiscussionThese findings revealed that long-term tooth loss is a chronic stressor, activating the recruitment of microglia and astrocytes; exacerbating neuroinflammation, Aβ deposition, phosphorylated tau accumulation, and synaptic dysfunction; and leading to spatial learning and memory impairments in AD model mice.https://www.frontiersin.org/articles/10.3389/fnagi.2024.1361847/fullAlzheimer’s diseasetooth lossamyloid-βphosphorylated taumicrogliaastrocyte |
| spellingShingle | Suzuko Ochi Kumiko Yamada Takashi Saito Takaomi C. Saido Mitsuo Iinuma Kagaku Azuma Kin-Ya Kubo Effects of early tooth loss on chronic stress and progression of neuropathogenesis of Alzheimer’s disease in adult Alzheimer’s model AppNL-G-F mice Frontiers in Aging Neuroscience Alzheimer’s disease tooth loss amyloid-β phosphorylated tau microglia astrocyte |
| title | Effects of early tooth loss on chronic stress and progression of neuropathogenesis of Alzheimer’s disease in adult Alzheimer’s model AppNL-G-F mice |
| title_full | Effects of early tooth loss on chronic stress and progression of neuropathogenesis of Alzheimer’s disease in adult Alzheimer’s model AppNL-G-F mice |
| title_fullStr | Effects of early tooth loss on chronic stress and progression of neuropathogenesis of Alzheimer’s disease in adult Alzheimer’s model AppNL-G-F mice |
| title_full_unstemmed | Effects of early tooth loss on chronic stress and progression of neuropathogenesis of Alzheimer’s disease in adult Alzheimer’s model AppNL-G-F mice |
| title_short | Effects of early tooth loss on chronic stress and progression of neuropathogenesis of Alzheimer’s disease in adult Alzheimer’s model AppNL-G-F mice |
| title_sort | effects of early tooth loss on chronic stress and progression of neuropathogenesis of alzheimer s disease in adult alzheimer s model appnl g f mice |
| topic | Alzheimer’s disease tooth loss amyloid-β phosphorylated tau microglia astrocyte |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1361847/full |
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