Cerebral dysfunction of offspring caused by stress during pregnancy can be improved by chewing

• Project/Area Number: 16K11819
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Asahi University
• Principal Investigator: IINUMA MITSUO 朝日大学, 歯学部, 教授 (70184364)
• Co-Investigator(Kenkyū-buntansha): 東 華岳 産業医科大学, 医学部, 教授 (20273146) ; 村林 知香 朝日大学, 歯学部, 助教 (50610367)
• 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 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 妊娠ストレス / 妊娠ストレス中の咀嚼 / 仔の脳機能障害 / 認知障害 / 情動障害 / ストレス脆弱脳 / 妊娠期ストレス / ストレス中の咀嚼 / 母胎ストレス / 仔マウス / 咀嚼 / シナプス後肥厚 / グルココルチコイドレセプター / 認知機能 / ミエリン鞘 / 超微細構造 / 咬合咀嚼刺激 / 情動認知 / オリゴデンドロサイト / シナプス

Outline of Final Research Achievements

We examined the effects of pregnancy stress and maternal chewing during pregnancy stress of offspring.　Mice were devided into three groups: control group, stress group and chewing group. Pregnancy stress induces the deficits in anxiety-like behavior and learning ability and cerebral function of offspring by increasing corticosterone levels in the dam. On the other hand cerebral dysfunction of offspring caused by pregnancy stress can be improved by maternal chewing. It was suggested chewing during pregnancy stress is an effective stress-coping method.

Academic Significance and Societal Importance of the Research Achievements

妊娠中は様々な面からストレスが加わることが多い。近年、妊娠中に強いストレス、或いは弱くても持続的なストレスに曝された母親から生まれた子供は、高次脳機能ネットワークの生後発達が遅延し、神経発達障害や精神疾患、情動障害のリスクが高まることが報告されている。
そこで今回、妊娠中の咀嚼運動がストレス対処法として有効であることを動物実験で明らかにし、ヒトにおいても妊娠中によく咬むことが子供の神経発達障害や精神疾患、情動障害の抑制に有効であることが示唆された。

Research Products

• [Journal Article] Chewing during prenatal stress prevents prenetal stress-induced suppression of neurogenesis, anzxiety-like behavior and learning deficits in mouse offspring (2018)
  • Author(s): Kin-ya-Kubo,Mika Kotachi, Ayumi Suzuki, Mitsuo Iinuma and Kagaku Azuma
  • Journal Title: Int.J. Med Sc Volume: 15 Pages: 849-858
  • Peer Reviewed / Open Access
• [Journal Article] Vulnerability to stress in mouse offspring is ameliorated when pregnant dams are provided a chewing stick during prenatal stress (2018)
  • Author(s): Kin-ya-Kubo Ayumi Suzuki, Mitsuo Iinuma Yuichi Sato Ryo Nagashio. Etsurou.ohta and Kagaku Azuma
  • Journal Title: Archives of Oral Biology Volume: 96 Pages: 1-11
  • Peer Reviewed / Open Access
• [Journal Article] Maternal occlusal disharmony during pregnancy induces spatial memory deficits associated with the suppression of hippocampal neurogenesis in adult mouse offspring (2017)
  • Author(s): Kondo H, Uchida M, Ichihashi M, Suzuki A, Hayashi S, Iinuma M, Azuma K and Kubo K
  • Journal Title: Pediatric Dental Journal Volume: 27 Issue: 1 Pages: 49-55
  • DOI: 10.1016/j.pdj.2016.12.002
  • Peer Reviewed / Open Access
• [Presentation] 妊娠母体の咀嚼が新生仔の海馬の神経系細胞数とアストロサイトに及ぼす影響 (2019)
  • Author(s): 片野正久、市橋幸子、宋本正文、越智鈴子、鈴木あゆみ、津金裕子、飯沼光生、東華岳、久保金弥
  • Organizer: 第５７回日本小児歯科学会大会：札幌
• [Presentation] Diabetes in adults mouse offspring ameliorated by maternal chewing during prenetal stress (2019)
  • Author(s): Sakurako Hayashi, Cie Hisada ,Hiroko Kondo, Kyoko Kajimoto, Masahisa Katano, Kumiko Yamada, Mitsuo Iinuma, Kagaku Azuma and Kin-ya Kubo
  • Organizer: 第27回国際小児歯科学会：メキシコカンクン
  • Int'l Joint Research
• [Presentation] 歯の早期喪失が海馬におけるミクログリアの発現に及ぼす影響 (2018)
  • Author(s): 近藤裕子, 久田智詠, 吉川英里, 梶本京子, 片野雅久, 林櫻子, 鈴木あゆみ, 飯沼光生, 山田久美子, 東華岳, 久保金弥
  • Organizer: 第55回日本小児歯科学会大会(大阪市）
• [Presentation] Maternal chewing ameliorates prenetal stress-induced hippocampal impairment in adult offspring (2018)
  • Author(s): Ayumi Suzuki,Hiroko Kondo,Mitsuo Iinuma,Kagaku Azuma and Kin-ya Kubo
  • Organizer: 96th IADR Meeting （London)
  • Int'l Joint Research
• [Presentation] Maternal chewing during prenatal stress in mice ameliorates stress-induced impairment of serotoninergic system in the adult offspring (2018)
  • Author(s): Kyoko Kajimoto, Ayumi Suzuki, Hiroko Kondo,Sakurako Hayashi, Masahisa Katano,Mitsuo Iinuma, Kagaku Azuma, Kin-ya Kubo
  • Organizer: 第41回日本神経科学学会(神戸市)
• [Presentation] 歯の早期喪失が海馬におけるミクログリアの発現に及ぼす影響 (2018)
  • Author(s): 近藤裕子, 久田智詠, 吉川英里, 梶本京子, 片野雅久, 林櫻子, 鈴木あゆみ, 飯沼光生, 山田久美子, 東華岳, 久保金弥
  • Organizer: 第５５回日本小児歯科学会
• [Presentation] Brain dysfunction is induced by the tooth loss (2017)
  • Author(s): Mitsuo Iinuma
  • Organizer: 第3回日本南アフリカ大学フォーラム
  • Int'l Joint Research
• [Presentation] 歯の喪失により惹起される脳機能障害は豊かな飼育環境により改善される (2016)
  • Author(s): 飯沼光生、鈴木あゆみ、林桜子、近藤裕子、村林知香、東華岳、久保金弥
  • Organizer: 第23回日本歯科医学会総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-10-21
• [Presentation] Maternal chewing during prenatal stress ameliorates stress-induced vulnerability of the brain to novel stress in the adult pups in mice (2016)
  • Author(s): 飯沼光生、鈴木あゆみ、林桜子、近藤裕子、村林知香、東華岳、久保金弥
  • Organizer: 第39回日本神経学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-07-20
• [Presentation] Maternal chewing during prenatal stress ameliorates stress-induced synaptic and myelin alterations in the hippocampus in adults pups (2016)
  • Author(s): Suzuki A,Hayashi S, Kondo H, Ogura M, MurabayashiC, KotachiM, Iinuma M, Azuma K and Kubo K
  • Organizer: 第10回アジア小児歯科学会
  • Place of Presentation: 東京ドームホテル
  • Year and Date: 2016-05-17
  • Int'l Joint Research