Study on mastication dysfunction-induced memory impairment

• Project/Area Number: 15K15712
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Nagoya City University
• Principal Investigator: Michikawa Makoto 名古屋市立大学, 大学院医学研究科, 教授 (40270912)
• Co-Investigator(Kenkyū-buntansha): 赤川 安正 奥羽大学, 歯学部, 教授 (00127599) ; 大上 博史 広島大学, 医歯薬保健学研究科(歯), 助教 (70711307) ; 小野 卓史 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30221857)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 認知症 / 歯牙欠損 / 咀嚼機能低下 / BDNF / 認知機能 / 歯科疾患 / 鼻閉 / 抜歯 / 粉末食 / 認知機能障害 / 神経細胞死

Outline of Final Research Achievements

The relationship between teeth loss or mastication dysfunction and dementia including Alzheimer’s disease has been reported. However, the molecular mechanism underlying these remain unknown. In this study we have examined teeth loss-induced and mastication dysfunction-induced memory impairment using mice and identified the mechanisms.

Research Products

• [Journal Article] Nasal obstruction during adolescence induces memory/learning impairments associated with BDNF/TrkB signaling pathway hypofunction and high corticosterone levels (2018)
  • Author(s): Ogawa Takuya、Okihara Hidemasa、Kokai Satoshi、Abe Yasunori、Karin Harumi Uchima Koecklin、Makiguchi Mio、Kato Chiho、Yabushita Tadachika、Michikawa Makoto、Ono Takashi
  • Journal Title: Journal of Neuroscience Research Volume: 96 Issue: 6 Pages: 1056-1065
  • DOI: 10.1002/jnr.24216
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory (2018)
  • Author(s): Yoshikawa Misato、Soeda Yoshiyuki、Michikawa Makoto、Almeida Osborne F. X.、Takashima Akihiko
  • Journal Title: Frontiers in Neuroscience Volume: 12 Pages: 124-124
  • DOI: 10.3389/fnins.2018.00124
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice (2017)
  • Author(s): Ishida N, Ishihara Y, Ishida K, Tada H, Funaki-Kato Y, Hagiwara M, Ferdous T, Abdullah M, Mitani A, Michikawa M, Matsushita K.
  • Journal Title: NPJ Aging Mech. Dis. Volume: 3 Issue: 1 Pages: 15-15
  • DOI: 10.1038/s41514-017-0015-x
  • NAID: 120006576159
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sodium balance, circadian BP rhythm, heart rate variability, and intrarenal renin-angiotensin-aldosterone and dopaminergic systems in acute phase of ARB therapy (2017)
  • Author(s): Isobe-Sasaki Yukako、Fukuda Michio、Ogiyama Yoshiaki、Sato Ryo、Miura Toshiyuki、Fuwa Daisuke、Mizuno Masashi、Matsuoka Tetsuhei、Shibata Hiroko、Ito Hiroyuki、Ono Minamo、Abe-Dohmae Sumiko、Kiyono Ken、Yamamoto Yoshiharu、Kobori Hiroyuki、Michikawa Makoto、Hayano Junichiro、Ohte Nobuyuki
  • Journal Title: Physiological Reports Volume: 5 Issue: 11 Pages: e13309-e13309
  • DOI: 10.14814/phy2.13309
  • Peer Reviewed / Open Access
• [Journal Article] Deficiency of a sulfotransferase for sialic acid-modified glycans mitigates Alzheimer's pathology. (2017)
  • Author(s): Zhang Z, Takeda-Uchimura Y, Foyez T, Ohtake-Niimi S, Narentuya, Akatsu H, Nishitsuji K, Michikawa M, Wyss-Coray T, Kadomatsu K, Uchimura K.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114(14) Issue: 14 Pages: 114-114
  • DOI: 10.1073/pnas.1615036114
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Aβ reduces exosome release from astrocytes by enhancing JNK phosphorylation (2016)
  • Author(s): Abdullah M, Takase H, Nunome M, Enomoto H, Ito J-I, Gong J-S, and Michikawa M.
  • Journal Title: J Alzhiemr Dis, Volume: 53 Issue: 4 Pages: 1433-1441
  • DOI: 10.3233/jad-160292
  • Peer Reviewed
• [Journal Article] Phosphatidylcholine protects neurons from toxic effects of amyloid β-protein in culture. (2016)
  • Author(s): Ko M, Hattori T, Abdullah M, Gong JS, Yamane T, Michikawa M.
  • Journal Title: Brain Res. Volume: 1642 Pages: 376-383
  • DOI: 10.1016/j.brainres.2016.04.035
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice. (2016)
  • Author(s): Takeda Y, Oue H, Okada S, Kawano A, Koretake K, Michikawa M, Akagawa Y, Tsuga K.
  • Journal Title: BMC Neurosci. Volume: ５ Issue: 1 Pages: 81-81
  • DOI: 10.1186/s12868-016-0319-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ABCG1 and ABCG4 Suppress γ-Secretase Activity and Amyloid β Production (2016)
  • Author(s): Osamu Sano, Maki Tsujita, Yuuji Shimizu, Reiko Kato, Aya Kobayashi, Noriyuki Kioka, Alan T Remaley, Makoto Michikawa, Kazumitsu Ueda, and Michinori Matsuo
  • Journal Title: PLoS One Volume: 11 Issue: 5 Pages: e0155400-e0155400
  • DOI: 10.1371/journal.pone.0155400
  • NAID: 120005997762
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tooth loss might not alter molecular pathogenesis in an aged transgenic Alzheimer's disease model mouse (2015)
  • Author(s): Oue H, Miyamoto Y, Koretake K, Okada S, Doi K, Jung CG, Michikawa M and Akagawa Y
  • Journal Title: Gerodontology Volume: in press Issue: 3 Pages: 308-14
  • DOI: 10.1111/ger.12153
  • Peer Reviewed
• [Journal Article] Arachidonic or docosahexaenoic acid diet prevents memory impairment in Tg2576 mice. (2015)
  • Author(s): Hosono T, Mouri A, Nishitsuji K, Jung CG, Kontani M, Tokuda H, Kawashima H, Shibata H, Suzuki T, Nabeshima T, Michikawa M.
  • Journal Title: J Alzheimers Dis Volume: 48 Issue: 1 Pages: 149-162
  • DOI: 10.3233/jad-150341
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Arachidonic Acid Diet Attenuates Aβ Deposition in Tg2576 Mice. (2015)
  • Author(s): Hosono T, Nishitsuji K, Nakamura T, Jung CG, Kontani M, Tokuda H, Kawashima H, Kiso Y, Suzuki T, Michikawa M
  • Journal Title: Brain Res Volume: 10 Pages: 1613-1629
  • DOI: 10.1016/j.brainres.2015.04.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Biochemical properties in membrane of rat astrocytes under oxidative stress. (2015)
  • Author(s): Ito J, Nagayasu Y, Ogawa T, Okihara H, Michikawa M.
  • Journal Title: Brain Res. Volume: 1615 Pages: 1-11
  • DOI: 10.1016/j.brainres.2015.04.008
  • Peer Reviewed
• [Journal Article] Lysophosphatidylcholine increases the neurotoxicity of Alzheimer's amyloid β1-42 peptide: role of oligomer formation. (2015)
  • Author(s): Sheikh AM, Michikawa M, Kim SU, Nagai A.
  • Journal Title: Neuroscience. Volume: 292 Pages: 159-69
  • DOI: 10.1016/j.neuroscience.2015.02.034
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] ATBF1 is a novel amyloid-β protein precursor protein (AβPP) binding protein that affects APP expression (2015)
  • Author(s): Uhm KO, Kim MJ, Kawaguchi M, Akatsu H, Miura Y, Misumi S, Hida H, Choi EK, Kim YS, Michikawa M, Jung CG.
  • Journal Title: J Alzheimers Dis Volume: 43 Issue: 1 Pages: 243-257
  • DOI: 10.3233/jad-140612
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Auraptene increases the production of amyloid-beta via c-Jun N-terminal kinase-dependent activation of γ-secretase. (2015)
  • Author(s): Jung CG, Uhm KO, Horike H, Kim MJ, Misumi S, Ishida A, Ued Y, Choi EK, Kim YS, Michikawa M, Hida H.
  • Journal Title: J Alzheimers Dis Volume: 43 Issue: 4 Pages: 1215-1228
  • DOI: 10.3233/jad-141692
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Angiotensin type 1a receptor deficiency decreases amyloid β-protein generation and ameliorates brain amyloid pathology. (2015)
  • Author(s): Liu J, Liu S, Matsumoto Y, Murakami S, Sugakawa Y, Kami A, Tanabe C, Maeda T, Michikawa M, Komano H, Zou K.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 12059-12059
  • DOI: 10.1038/srep12059
  • Peer Reviewed / Open Access
• [Presentation] 歯周病、咀嚼機能低下がアルツハイマー病分病態ならびに認知機能に及ぼす影響 (2016)
  • Author(s): 道川 誠
  • Organizer: 第6回日本認知症予防学会
  • Place of Presentation: 東北大学（宮城県、仙台市）
  • Year and Date: 2016-09-23
• [Presentation] 認知症の正しい理解と歯科・口腔疾患との関連 (2016)
  • Author(s): 道川 誠
  • Organizer: 第61回日本口腔外科学会総会
  • Place of Presentation: 幕張メッセ（千葉県、千葉市）
  • Invited
• [Presentation] Arachidonic or docosahezanenoic acid diet attenuates Ab deposition and prevents memory impairment in Tg2576 mice. (2015)
  • Author(s): Makoto Michikawa
  • Organizer: Aging and Neurodegenerative Disease. 2015 Ilsong Mini Symposium. Korea
  • Place of Presentation: 韓国
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] 認知症と脂質異常症・血管性要因 (2015)
  • Author(s): 道川 誠
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: リンクステーションホール（青森県青森市）
  • Year and Date: 2015-10-02
• [Presentation] 歯周病・咀嚼機能低下がアルツハイマー病分子病態・認知機能に及ぼす影響 (2015)
  • Author(s): 道川 誠
  • Organizer: 日本歯科大学新潟生命歯学科
  • Place of Presentation: 日本歯科大学新潟生命歯学部（新潟県新潟市）
  • Year and Date: 2015-09-07
  • Invited
• [Presentation] 特別講演：認知症の正しい理解と歯科医療との関わりにおける最新知見 (2015)
  • Author(s): 道川 誠
  • Organizer: 日本歯科大学公開フォーラム
  • Place of Presentation: 日本歯科大学（東京都千代田）
  • Year and Date: 2015-09-06
  • Invited
• [Presentation] 特別講演：歯周病・咀嚼機能低下がアルツハイマー病分子病態・認知機能に及ぼす影響 (2015)
  • Author(s): 道川 誠
  • Organizer: 北海道医療大学招待講演
  • Place of Presentation: 北海道医療大学（北海道石狩郡当別町）
  • Year and Date: 2015-07-28
  • Invited
• [Book] 歯科と認知症 (2015)
  • Author(s): 道川 誠、平野浩彦、吉岡裕雄、福井智子、白野美和、須田牧夫
  • Total Pages: 110
  • Publisher: メディア出版