公募シンポジウム

公募シンポジウム口腔疾患がアルツハイマー病分子病態に及ぼす影響の分子メカニズムの検討

7月6日（木）　14:20-16:20　Room E 1SY⑥-1 歯牙欠損はアルツハイマー病分子病態を促進させる Tooth loss exacerbates molecular pathogenesis in Alzheimer's disease. 鄭　且均, 道川　誠名古屋市立大学大学院医学研究科神経生化学 Cha-Gyun Jung, Makoto Michikawa Dept. of Biochemistry, Graduate School of Medical Sciences, Nagoya City Univ.,Nagoya, Japan Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease. AD is pathologically characterized by the presence of amyloid-β plaques and neurofibrillary tangles. Oral health is essential for maintaining general health and well-being in every stage of life. Tooth loss due to dental caries and periodontitis can trigger or exacerbate diseases such as diabetes, other inflammatory diseases, and AD. Although epidemiological studies have shown that tooth loss is associated with AD and dementia, the molecular and cellular mechanisms by which tooth loss causes AD remain unclear. We investigated the effects of tooth loss on memory impairment and AD pathogenesis in App^NL-G-F and wild-type mice. Tooth loss induced memory impairment, and decreased the neuronal activity, presynaptic and postsynaptic protein levels in both the cortex and hippocampus. Interestingly, we found that tooth loss induced glial activation, which in turn leads to the upregulation of the mRNA expression levels of the neuroinflammation cytokines TNF-α, IL-6, and IL-1β in the hippocampus. We also found that tooth loss activated a stress-activated protein kinase, JNK and increased HSP90 levels, which may lead to a glial activation. Our findings suggest that taking care of teeth is very important to preserve a healthy oral environment, which may reduce the risk of cognitive dysfunction.		7月6日（木）　14:20-16:20　Room E 1SY⑥-2 三叉神経のオートファジーとアルツハイマー病進行との関連について The relationship between trigeminal autophagy and Alzheimer's disease progression. 後藤　哲哉鹿児島大学大学院医歯学総合研究科　歯科機能形態学分野 Tetsuya Goto Dept. of Oral Anat. and Cell Biol., Kagoshima University, Japan Although a relationship between oral dysfunction and the development of Alzheimer's disease (AD) in the elderly has been suggested, the histopathological relationship between aging or neurodegeneration of the trigeminal nervous system and the accumulation of amyloid-β Aβ(1-42) (Aβ)₄₂ oligomers in the pathogenesis of AD has remained unclear. We focused on selective autophagy and Aβ₄₂ oligomer diffusion in the trigeminal mesencephalic nucleus (Vmes) with respect to aging of the trigeminal nervous system to determine whether aging or degeneration of Vmes neurons affects Aβ₄₂ oligomer diffusion. 2∽8-month-old female transgenic 3xTg-AD mice and App^NL-G-F knock-in mice were used to examine temporal changes in molecules involved in selective autophagy and aging in the Vmes, which shows high Aβ expression. While in App^NL-G-F mice, extracellular Aβ₄₂ oligomers were abundant and Aβ₄₂ oligomer clusters were formed, in Vmes neurons of AD model mice, the expression of Rubicon indicates age-related degradation of autophagy increased with age. These results suggest that autophagy maintains homeostasis in Vmes neurons, and that age-related degradation of autophagy may cause Aβ₄₂ oligomers to diffuse out of the cells, leading to AD development.

7月6日（木）　14:20-16:20　Room E 1SY⑥-3 The potential oral-gut-brain axis and Alzheimer's disease 安彦　善裕北海道医療大学　歯学部　臨床口腔病理学分野 Yoshihiro Abiko Oral Medicine & Pathology, School of Dentistry, Health Sciences University of Hokkaido The oral-gut-brain axis is a theoretical concept rather than a materialized anatomical axis like the gut-brain axis. The idea of a microbiota oral-gut-brain axis is guided by evidence from each of the three components of the axis; oral-brain axis, gut-brain axis, and communication between the oral and gut microbiota. Alzheimer’s disease(AD) has been complicated by its enigmatic and multifactorial nature. The deposition of amyloid-beta (Aβ) protein are typical pathological features in AD patients. Dysbiosis of oral and gut microbiota has been reported to induce and accelerate the formation of Aβ plaques.We introduce our recent work about the oral-gut-brain axis possibly related to AD as follows.1) Lipopolysaccharide (LPS) derived from P. gingivalis (PG) decreases neprilysin enzyme that degrade Aβ deposition. 2) Oral of PG negatively alters gut microbiome, of which is more pronounced with increasing aging. 3) Psychological stress negatively alters oral and gut microbiota, and many of the negative oral microbe may translocate to gut. These results suggest that the oral-gut-brain axis may be partially involved in AD.		7月6日（木）　14:20-16:20　Room E 1SY⑥-4 口腔の健康と認知症の関連性の探索 Exploring the Association Between Oral Health and Dementia 松下　健二長寿センター　口腔疾患 Kenji Matsushita Dept. of Oral Dis. Res., NCGG, Obu, Japan The smaller number of retained teeth is, the lower is the cognitive function and the higher is the risk of developing dementia. We have recently shown that extraction of the first maxillary upper molars in aged mice and AD model mice and long-term rearing of aged mice on a soft diet decreased spontaneous activity, spatial working memory, and motor coordination and enhanced cellular senescence in the hippocampus and hypothalamus. Recently, a number of epidemiological and animal studies have shown that periodontal disease and the periodontopathic bacterium Porphyromonas gingivalis are associated with cognitive function and dementia. In mouse models, P. gingivalis infection impairs cognitive function and promotes the deposition of amyloid-β protein (Aβ) in the brain. Furthermore, inhibition of gingipain has been shown to improve the pathogenesis of AD in mouse models. Recently, clinical trials (Phase II/III) of AD treatment with gingipain inhibitors were conducted in Europe and the United States, and their efficacy was partially confirmed. In this presentation, Periodontal disease, oral bacteria, oral function, and dementia/Alzheimer's disease are the keywords, and we will discuss the importance of oral health for extending healthy life expectancy.