Role of mother-pup interaction in the development of brain and behavior

• Project/Area Number: 17K08487
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: University of Tsukuba
• Principal Investigator: Shiga Takashi 筑波大学, 医学医療系, 教授 (50178860)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 母子関係 / 養育行動 / 皮膚刺激 / 環境要因 / 記憶学習 / うつ様行動 / セロトニン / 行動の発達

Outline of Final Research Achievements

The formation of neural network is not only genetically programmed but also modulated by various environmental factors during development. In this study, we showed that mother-pup interactions and tactile stimulation modulate development of brain and behavior. While short term maternal separation and tactile stimulation gave positive effects on the development of behavior, long term maternal separation negative effects. We next showed that serotonin 1A receptor, GABA-A a2 receptor, and brain-derived neurotrophic factor in the hippocampus and amygdala may be involved in mediating the effects of environmental factors on the behavior.

Academic Significance and Societal Importance of the Research Achievements

脳と行動の発達に影響を及ぼす環境要因として肉体的・精神的な陰性ストレス（いわゆるストレス）の研究が進んでいる。一方、良い影響を与える環境要因（広義の陽性ストレス）の神経科学的アプローチは遅れている。本研究では、生後発達期の養育行動と皮膚刺激の役割を解析した。このような研究は限られており、発達期の脳の構造と機能の可塑性の観点からも重要である。さらに皮膚刺激はタッチケアとしてヒト新生児（特に未熟児）に対して推奨されているが、その作用の脳内機構は全く不明であり、十分な科学的裏付けがない。本研究によってヒトのタッチケアの動物モデルの確立とタッチケアの脳内機構の解明への貢献が期待される。

Research Products

• [Int'l Joint Research] Southwest University(中国)
• [Int'l Joint Research] Harvard Medical School(米国)
• [Journal Article] Therapeutic potential of serotonin 4 receptor for chronic depression and its associated comorbidity in the gut. (2020)
  • Author(s): Agrawl L, Korkutata M, Vimal SK, Yadav MK, Bhattacharyya S, Shiga T.
  • Journal Title: Neuropharmacology Volume: 166 Pages: 107969-107969
  • DOI: 10.1016/j.neuropharm.2020.107969
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Role of serotonin 4 receptor in the growth of hippocampal neurons during the embryonic development in mice. (2019)
  • Author(s): Agrawal L, Vimal SK, Shiga T.
  • Journal Title: Neuropharmacology Volume: 158 Pages: 107712-107712
  • DOI: 10.1016/j.neuropharm.2019.107712
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Primary cultured neuronal networks and type 2 diabetes model mouse fatty liver tissues in aqueous liquid observed by atmospheric SEM (ASEM): Staining preferences of metal solutions (2019)
  • Author(s): Sato Chikara、Yamazawa Toshiko、Ohtani Akiko、Maruyama Yuusuke、Memtily Nassirhadjy、Sato Mari、Hatano Yuri、Shiga Takashi、Ebihara Tatsuhiko
  • Journal Title: Micron Volume: 118 Pages: 9-21
  • DOI: 10.1016/j.micron.2018.11.005
  • Peer Reviewed / Open Access
• [Journal Article] Effects of postnatal handling on adult behavior and brain mRNA expression of serotonin receptor, brain-derived neurotrophic factor and GABA-A receptor subunit (2018)
  • Author(s): Li Haiyan、Ishikawa Chihiro、Shiga Takashi
  • Journal Title: International Journal of Developmental Neuroscience Volume: 68 Issue: 1 Pages: 17-25
  • DOI: 10.1016/j.ijdevneu.2018.04.002
  • NAID: 120007133747
  • Peer Reviewed
• [Journal Article] An idea of using microneedles for the targeted drug delivery to overcome the blood brain barrier for the treatment of brain diseases. (2018)
  • Author(s): Agrawal L, Vimal SK, Chen M-H, Shiga T
  • Journal Title: J Pharmacovigilance Volume: 6 Issue: 05 Pages: 1000270-1000270
  • DOI: 10.4172/2329-6887.1000270
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The postnatal 5-HT1A receptor regulates adult anxiety and depression differently via multiple molecules (2017)
  • Author(s): Ishikawa C, Shiga T
  • Journal Title: Progress in neuro-psychopharmacology and biological psychiatry. Volume: 78 Pages: 66-74
  • DOI: 10.1016/j.pnpbp.2017.04.014
  • NAID: 120007128897
  • Peer Reviewed
• [Presentation] Promotion of axon and dendrites formation by serotonin 4 receptor through collapsing response mediator protein-2 (2019)
  • Author(s): Agrawal L, Shiga T.
  • Organizer: Society for Neuroscience (SFN) meeting 2019
  • Int'l Joint Research
• [Presentation] 陽性ストレスによるラット脳内D-アミノ酸濃度の変動解析 (2019)
  • Author(s): 下地康介、石田哲夫、志賀隆
  • Organizer: 第92回日本生化学会大会
• [Presentation] 慢性的な陽性ストレスがラット脳内アミノ酸代謝に与える影響 (2019)
  • Author(s): 下地康介、石田哲夫、志賀隆
  • Organizer: 第 107 回日本解剖学会関東支部学術集会
• [Presentation] In vitro study of role of serotonin 4 receptor in neurite formation of hippocampal neurons (2018)
  • Author(s): Agrawal L, Shiga T.
  • Organizer: 第106回日本解剖学会関東支部会
• [Presentation] 5-HT4R mediated expression of CRMP2 to control the growth of neurites in hippocampal neurons in vitro (2018)
  • Author(s): Agrawal L, Shiga T.
  • Organizer: International Conference, Tsukuba Global Science Week
  • Int'l Joint Research
• [Presentation] 生後発達期のセロトニン神経系が脳と行動の発達に及ぼす影 (2018)
  • Author(s): 志賀 隆、李 海燕、石川千尋
  • Organizer: 第123回日本解剖学会全国学術集会
• [Presentation] Roles of 5-HT4 receptor on dendritic development of cortical neurons. (2017)
  • Author(s): Kasegai H, Shiga T.
  • Organizer: TGSW(Tsukuba Global Science Week)2017
• [Remarks] 筑波大学医学医療系神経生物学グループ
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/shiga-group/anatomy3rd.html