| First Author | Sonoda R | Year | 2023 |
| Journal | J Dent Res | Volume | 102 |
| Issue | 8 | Pages | 938-946 |
| PubMed ID | 36919893 | Mgi Jnum | J:350716 |
| Mgi Id | MGI:7664197 | Doi | 10.1177/00220345231156095 |
| Citation | Sonoda R, et al. (2023) Reduced Autophagy in Aged Trigeminal Neurons Causes Amyloid beta Diffusion. J Dent Res 102(8):938-946 |
| abstractText | 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-beta(1-42) (Abeta(42)) oligomers in the pathogenesis of AD is unknown. We focused on selective autophagy in the trigeminal mesencephalic nucleus (Vmes) and the diffusion of Abeta(42) oligomers with respect to aging of the trigeminal nervous system and whether the degeneration of Vmes neurons affects the diffusion of Abeta(42) oligomers. We used female 2- to 8-mo-old transgenic 3xTg-AD mice and App(NL-G-F) knock-in mice and immunohistochemically examined aging-related changes in selective autophagy and Abeta(42) oligomer processing in the Vmes, which exhibits high amyloid-beta (Abeta) expression. We induced degeneration of Vmes neurons by extracting the maxillary molars and examined the changes in Abeta(42) oligomer kinetics. Autophagosome-like membranes, which stained positive for Abeta, HO-1, and LC3B, were observed in Vmes neurons of 3xTg-AD mice, while there was weak immunoreactivity of the membranes for intraneuronal Abeta in App(NL-G-F) mice. By contrast, there was strong immunopositivity for extracellular Abeta(42) oligomers with the formation of Abeta(42) oligomer clusters in App(NL-G-F) mice. The expression of Rubicon, which indicates age-related deterioration of autophagy, increased the diffusion of Abeta(42) oligomer with the age of Vmes neurons. Tooth extraction increased the extracellular immunopositivity for Abeta(42) oligomers in App(NL-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 Abeta(42) oligomers into the extracellular space and possibly the development of AD. |
