Mechanisms inducing cognitive dysfunction following occlusion/mastication disorder: Analyses of neural circuits around mesencephalic trigeminal nucleus

• Project/Area Number: 16K11482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kagoshima University
• Principal Investigator: Saito Mitsuru 鹿児島大学, 医歯学域歯学系, 教授 (50347770)
• Co-Investigator(Kenkyū-buntansha): 倉本 恵梨子 鹿児島大学, 医歯学域歯学系, 助教 (60467470)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 認知症 / 咀嚼障害 / 三叉神経中脳路核 / 青斑核 / 閉口筋筋紡錘 / 歯根膜機械受容器 / 神経栄養因子 / 筋紡錘 / 歯根膜 / 栄養因子 / 咬合支持崩壊 / 前脳基底部 / Onecut因子 / シナプス伝達 / グルタミン酸 / AMPA型受容体 / Hチャネル / 微小ドメイン / 咀嚼運動 / 歯根膜感覚 / 閉口筋筋紡錘感覚 / 生理学 / 口腔生理学 / 歯学 / 咬合 / 高次脳機能

Outline of Final Research Achievements

Many studies indicate that the infection of periodontal disease-causing bacteria is a risk factor of Alzheimer disease and dementia, while a lot of epidemiological studies suggest that mastication disorder could induce cognitive dysfunction regardless of the presence or absence of periodontal disease. The mastication disorder causes activity decline and/or death of the neurons of the mesencephalic trigeminal nucleus (MTN) innervating jaw-closer muscle spindles and periodontal mechanoreceptors. In this study, we investigated the mechanisms inducing the cognitive dysfunction following the impairment of the MTN. It is suggested that the MTN impairment leads to activity decline and/or death of the neurons of the locus coeruleus which locates near the MTN, and that this is not mediated by the synaptic connections between the neurons of the two nuclei.

Academic Significance and Societal Importance of the Research Achievements

医療の発達により平均寿命が延長している中、高齢者における認知症発症が重大な問題となっており、その抑制が医学が果たすべき重大な使命のひとつとなっている。歯周病菌への感染がアルツハイマー病とそれによる認知症の発症の危険因子であることを示す報告は数多くある。一方で、歯周病への感染が無くとも、多数歯の脱落等によって食物を十分に咀嚼しない状態が継続すると、閉口筋筋紡錘や歯根膜機械受容器を支配している三叉神経中脳路核ニューロンが障害され、更にそれが青斑核ニューロンの異常に繋がることで、学習・記憶等の認知機能の低下を惹き起こすことが示唆される。

Research Products

• [Int'l Joint Research] ソウル大学(韓国)
• [Int'l Joint Research] ソウル大学/慶北大学(韓国)
• [Int'l Joint Research] ソウル大学/慶北大学(韓国)
• [Journal Article] Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABAA Receptors with a Special Reference to Propofol/Barbiturate (2020)
  • Author(s): Kang Youngnam、Saito Mitsuru、Toyoda Hiroki
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 2 Pages: 563-563
  • DOI: 10.3390/ijms21020563
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of GluR Current in Microvilli of Sensory Neurons via Na(+)-Microdomain Coupling among GluR, HCN channel and Na(+)/K(+) Pump. (2018)
  • Author(s): Kawasaki Y, Saito M, Won J, Bae JY, Sato H, Toyoda H, Kuramoto E, Kogo M, Tanaka T, Kaneko T, Oh SB, Bae YC, Kang Y.
  • Journal Title: Front. Cell. Neurosci. Volume: 印刷中 Pages: 113-113
  • DOI: 10.3389/fncel.2018.00113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Electrophysiological and Morphological Properties of α and γ Motoneurons in the Rat Trigeminal Motor Nucleus (2018)
  • Author(s): Nishimura K, Ohta M, Saito M, et al.
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 12 Pages: 9-9
  • DOI: 10.3389/fncel.2018.00009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A distinct functional distribution of α and γ motoneurons in the rat trigeminal motor nucleus. (2017)
  • Author(s): Morita-Isogai, Y., Sato, H., Saito, M., Kuramoto, E., Yin, D., Kaneko, T., Yamashiro, T., Takada, K., Oh, S.B., Toyoda, H., & Kang, Y.
  • Journal Title: Brain Structure and Function Volume: - Issue: 7 Pages: 1-9
  • DOI: 10.1007/s00429-017-1400-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Possible Role of TASK Channels in Rank-Ordered Recruitment of Motoneurons in the Dorsolateral Part of the Trigeminal Motor Nucleus. (2016)
  • Author(s): Okamoto K, Emura N, Sato H, Fukatsu Y, Saito M, Tanaka C, Morita Y, Nishimura K, Kuramoto E, Xu Yin D, Furutani K, Okazawa M, Kurachi Y, Kaneko T, Maeda Y, Yamashiro T, Takada K, Toyoda H, Kang Y.
  • Journal Title: eNeuro Volume: 3(3) Issue: 3 Pages: 3-3
  • DOI: 10.1523/eneuro.0138-16.2016
  • Peer Reviewed / Open Access
• [Journal Article] A role of CB1R in inducing θ-rhythm coordination between the gustatory and gastrointestinal insula. (2016)
  • Author(s): Kang, Y., Sato, H., Saito, M.,Yin, D., Park, S.K., Oh, S.B., Bae, Y.C. & Toyoda, H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 32529-32529
  • DOI: 10.1038/srep32529
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 副腎皮質刺激ホルモン放出ホルモンの脳内投与が顎機能に及ぼす影響 (2018)
  • Author(s): 八木 孝和, 齋藤 充, 後藤 哲哉, 小柳 宏太郎, 菅 真有, 宮脇 正一
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] アルツハイマー病モデルマウスにおける三叉神経系の神経変性が咀嚼機能に与える影響 (2018)
  • Author(s): 八木 孝和, 倉本 恵梨子, 関 遥, 齋藤 充, 岩井 治樹, 山中 淳之, 後藤 哲哉
  • Organizer: 第60回歯科基礎医学会学術大会