並列タイトル等Reduced Autophagy in Aged Trigeminal Neurons Causes Amyloid β Diffusion
学位博士(歯学)
Doctor of Philosophy in Dental Science
一般注記博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
The relationship between oral health and the development of Alzheimer’s disease (AD) in the elderly is not yet well understood. In this regard, the association between aging or neurodegeneration of the trigeminal nervous system and the accumulation of amyloid-β(1–42) (Aβ42) oligomers in the pathogenesis of AD is unknown. We focused on selective autophagy in the trigeminal mesencephalic nucleus (Vmes) and the diffusion of Aβ42 oligomers with respect to aging of the trigeminal nervous system and whether the degeneration of Vmes neurons affects the diffusion of Aβ42 oligomers. We used female 2- to 8-mo-old transgenic 3xTg-AD mice and AppNL-G-F knock-in mice and immunohistochemically examined aging-related changes in selective autophagy and Aβ42 oligomer processing in the Vmes, which exhibits high amyloid-β (Aβ) expression. We induced degeneration of Vmes neurons by extracting the maxillary molars and examined the changes in Aβ42 oligomer kinetics. Autophagosome-like membranes, which stained positive for Aβ, HO-1, and LC3B, were observed in Vmes neurons of 3xTg-AD mice, while there was weak immunoreactivity of the membranes for intraneuronal Aβ in AppNL-G-F mice. By contrast, there was strong immunopositivity for extracellular Aβ42 oligomers with the formation of Aβ42 oligomer clusters in AppNL-G-F mice. The expression of Rubicon, which indicates age-related deterioration of autophagy, increased the diffusion of Aβ42 oligomer with the age of Vmes neurons. Tooth extraction increased the extracellular immunopositivity for Aβ42 oligomers in AppNL-G-F mice. These results suggest that autophagy maintains homeostasis in Vmes neurons and that deterioration of autophagy due to aging or neurodegeneration leads to the diffusion of Aβ42 oligomers into the extracellular space and possibly the development of AD.R. Sonoda, E. Kuramoto, S. Minami, S.E. Matsumoto, Y. Ohyagi, T. Saito, T. Saido, K. Noguchi, and T. GotoReduced Autophagy in Aged Trigeminal Neurons Causes Amyloid β DiffusionJournal of Dental ResearchCopyright © 2023 International Association for Dental Research and American Association for Dental, Oral, and Craniofacial Research.https://doi.org/10.1177/00220345231156095
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受理日（W3CDTF）2023-07-08T03:42:30+09:00
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