鹿児島大学 · 医歯学総合研究科 · 准教授

研究キーワードtrigeminal ganglion・orofacial neuropathic pain・oral frailty・tooth development・heterodont dentition・house shrew model・trigeminal mesencephalic neurodegeneration・craniofacial evolution

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• Goto T., Kuramoto E., Iwai H., Yamanaka A. . Cytoarchitecture and intercellular interactions in the trigeminal ganglion: Associations with neuropathic pain in the orofacial region . Jo2024 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Journal of Oral Biosciences Background: Disorders of the trigeminal nerve, a sensory nerve of the orofacial region, often lead to complications in dental practice, including neuropathic pain, allodynia, and ectopic pain. Management of these complications requires an understanding of the cytoarchitecture of the trigeminal ganglion, where the cell bodies of the trigeminal nerve are located, and the mechanisms of cell-cell interactions. Highlights: In the trigeminal ganglion, ganglion, satellite, Schwann, and immune cells coexist and interact. Cell-cell interactions are complex and occur through direct contact via gap junctions or through mediators such as adenosine triphosphate, nitric oxide, peptides, and cytokines. Interactions between the nervous and immune systems within the trigeminal ganglion may have neuroprotective effects during nerve injury or may exacerbate inflammation and produce chronic pain. Under pathological conditions of the trigeminal nerve, cell-cell interactions can cause allodynia and ectopic pain. Although cell-cell interactions that occur via mediators can act at some distance, they are more effective when the cells are close together. Therefore, information on the three-dimensional topography of trigeminal ganglion cells is essential for understanding the pathophysiology of ectopic pain. Conclusions: A three-dimensional map of the somatotopic localization of trigeminal ganglion neurons revealed that ganglion cells innervating distant orofacial regions are often apposed to each other, interacting with and potentially contributing to ectopic pain. Elucidation of the complex network of mediators and their receptors responsible for intercellular communication within the trigeminal ganglion is essential for understanding ectopic pain. DOI： 10.1016/j.job.2024.07.003 Scopus PubMed
• Yamanaka A. . Evolution and development of the mammalian multicuspid teeth . Journal of Oral Biosciences64 ( 2 ) 165 - 175 22022 · 担当区分： 筆頭著者, 責任著者 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Journal of Oral Biosciences Background: Mammalian premolars and molars (cheek teeth) are teeth with multiple cusps, which are important characteristics of mammals. Endothermic mammals have high basal metabolic rates and must take in much energy by efficient mastication of food using their multicuspid cheek teeth. From the phylogenetic (evolutionary) perspective, the mammalian multicuspid teeth are derived from the reptilian unicuspid teeth with a single cone by adding new cusps around the original cone. Nearly 100 million years of long geological time were required for the unicuspid tooth to transform into a tribosphenic molar, which is the prototype of all molars in modern mammals. From the ontogenetic (developmental) perspective, the shape of the tooth germ becomes complex by adding the secondary enamel knots repeatedly in a short embryonic period. The secondary enamel knots are signaling centers that determine the future cusp positions. Highlight: Here we first reviewed the evolutionary process of the tribosphenic molar in the Mesozoic Era (the age of dinosaurs), and cusp homologies in the fossil record. Next, we reviewed the developmental mechanisms controlling the patterning of secondary enamel knots, which determine the final cusp patterns of molars in modern mammals. Finally, we discussed the possible relationship between the two processes from the extremely different time scales. Conclusion: A parallel relationship between ontogeny and phylogeny of the mammalian multicuspid teeth was expected. DOI： 10.1016/j.job.2022.03.007 Scopus PubMed
• Kuramoto E., Kitawaki A., Yagi T., Kono H., Matsumoto S.E., Hara H., Ohyagi Y., Iwai H., Yamanaka A., Goto T. . Development of a system to analyze oral frailty associated with Alzheimer's dise2022 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Frontiers in Aging Neuroscience The rapid aging of the population makes the detection and prevention of frailty increasingly important. Oral frailty has been proposed as a novel frailty phenotype and is defined as a decrease in oral function coexisting with a decline in cognitive and physical functions. Oral frailty has received particular attention in relation to Alzheimer's disease (AD). However, the pathomechanisms of oral frailty related to AD remain unknown. It is assumed that the mesencephalic trigeminal nucleus (Vmes), which controls mastication, is affected by AD pathology, and as a result, masticatory function may be impaired. To investigate this possibility, we included male 3 × Tg-AD mice and their non-transgenic counterpart (NonTg) of 3–4 months of age in the present study. Immunohistochemistry revealed amyloid-β deposition and excessive tau phosphorylation in the Vmes of 3 × Tg-AD mice. Furthermore, vesicular glutamate transporter 1-immunopositive axon varicosities, which are derived from Vmes neurons, were significantly reduced in the trigeminal motor nucleus of 3 × Tg-AD mice. To investigate whether the AD pathology observed in the Vmes affects masticatory function, we analyzed electromyography of the masseter muscle during feeding. The 3 × Tg-AD mice showed a significant delay in masticatory rhythm compared to NonTg mice. Furthermore, we developed a system to simultaneously record bite force and electromyography of masseter, and devised a new method to estimate bite force during food chewing in mice. Since the muscle activity of the masseter showed a high correlation with bite force, it could be accurately estimated from the muscle activity. The estimated bite force of 3 × Tg-AD mice eating sunflower seeds was predominantly smaller than that of NonTg mice. However, there was no difference in masseter weight or muscle fiber cross-sectional area between the two groups, suggesting that the decreased bite force and delayed mastication rhythm observed in 3 × Tg-AD mice were not due to abnormality of the masseter. In conclusion, the decreased masticatory function observed in 3 × Tg-AD mice was most likely caused by AD pathology in the Vmes. Thus, novel quantitative analyses of masticatory function using the mouse model of AD enabled a comprehensive understanding of oral frailty pathogenesis. DOI： 10.3389/fnagi.2022.935033 Scopus PubMed
• Yamanaka A, Iwai H, Uemura M, Goto T2015 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌）

• 人類進化過程における歯種の形態変化の源流をたどる～スンクスを用いたQTL解析～2022 · 配分額： 4290000円 （ 直接経費： 3300000円 、 間接経費： 990000円 ）
• 味蕾基底細胞の再定義：「細胞型分化の解明」と「味蕾オルガノイド評価系の確立」2020 · 配分額： 4290000円 （ 直接経費： 3300000円 、 間接経費： 990000円 ） 味蕾のI、II、III型細胞は味受容機能が異なり、五基本味のうち甘味・うま味・苦味はII型細胞、酸味はIII型細胞が受容する。塩味は濃度によって受容細胞が異なり、低濃度の塩味はI型細胞の一部、高濃度の塩味はII型とIII型細胞の一部が受容するとされている。各味蕾内の細胞型の構成比は、I型が全細胞の約半数程度と最も多く、次いでII型が多く、III型細胞は最も少ないとされる。この比率には味蕾が存在する口腔内の部位ごとに差があり、III型細胞の割合は有郭乳頭で最も高く、軟口蓋、茸状乳頭の順に少ないとされている。味蕾幹細胞を培養して形成されるオルガノイド内には、幹細胞を採取する口腔内部位に対応した割合で各細胞型が分化するという報告がある。しかし、実際は、生体における個々の味蕾の細胞構成は充分には検討されていない。また細胞型の分類に使用される分子マーカーにも、検討が不十分な分子がある。 本研究では、味蕾の形態を維持したままホールマウント免疫染色を行い、個々の味蕾の II型とIII型の細胞構成を詳細に解析した。その結果、1) 抗3型イノシトール三リン酸受容体 (IP3R3) 抗体で検出されるII型細胞と抗4型炭酸脱水酵素 (CA4)抗体で検出されるIII型細胞は、完全に独立しており、これらの分子の細胞型マーカーとしての信頼性が確認された。2) 一方、これらの分子マーカーで検出されるII型とIII型細胞の数は、味蕾間で大きくばらついており、特に茸状乳頭と軟口蓋の味蕾では従来提唱されてきた相関関係は検出されなかった。さらに、III型細胞マーカーとされているNCAMを加えて解析したところ、CA4を発現する細胞はすべてNCAMを発現すること、また、軟口蓋と茸状乳頭の味蕾では、CA4を発現しないNCAM発現細胞の中にII型細胞マーカーであるIP3R3を発現する細胞が存在することが、明らかになった。
• Shhシグナルによるアクトミオシン細胞内張力を介した歯の形態形成の新たな制御機構2019 · 2019年4月 - 2022年3月
• 非筋型ミオシンIIが歯の幹細胞ニッチの形成とエナメル芽細胞の移動に果たす役割2016 · 2016年4月 - 2019年3月

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