The role of sex hormones in brain morphogenesis and sex differentiation

• Project/Area Number: 26460258
• 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: Aichi Gakuin University
• Principal Investigator: Komada Munekazu 愛知学院大学, 歯学部, 助教 (90523994)
• Co-Investigator(Kenkyū-buntansha): 池田 やよい 愛知学院大学, 歯学部, 教授 (00202903)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: エストロゲン / 神経新生 / 大脳皮質 / 視床下部 / ビスフェノールA / ミクログリア / Steroidogenic factor-1 / 神経分化 / 神経炎症 / 性分化 / 性ホルモン / Steroidogenic factor 1 / 細胞移動

Outline of Final Research Achievements

Estrogen receptors express in the neurons and microglia in the brain and regulate their activity. Neurosteroids are converted by aromatase and are involved in the development and maturation of the brain. In the study, we showed that SF-1, regulated the expression of estrogen-producing enzyme, were expressed in the neocortex and the brain derived estrogen controlled the proliferation, differentiation, and migration of neurons. In addition, toxicity evaluation by the prenatal exposure of estrogenic chemical substances resulted in the abnormalities in the hypothalamus construction, brain-inflammation, and increase of microglia. We suggest that estrogen signaling act on the neurons and microglia, and contribute to the proper development of brain.

Research Products

• [Journal Article] Filamin A interacting protein plays a role in proper positioning of callosal projection neurons in the cortex (2016)
  • Author(s): Yagi H, Oka Y, Komada M, Xie MJ, Noguchi K, Sato M.
  • Journal Title: Neurosci Lett Volume: 612 Pages: 18-24
  • DOI: 10.1016/j.neulet.2015.11.049
  • Peer Reviewed / Open Access
• [Journal Article] Extraction of DNA from human embryos after long-term preservation in formalin and Bouin’s solutions. (2016)
  • Author(s): Nagai M, Minehishi K, Komada M, Tsuchiya M, Kameda T, Yamada S.
  • Journal Title: Congenit Anom (Kyoto) Volume: 56(3) Issue: 3 Pages: 112-8
  • DOI: 10.1111/cga.12148
  • NAID: 130008079243
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression of Kisspeptin in gonadotrope precursors in the mouse pituitary during embryonic and postnatal development and in adulthood. (2016)
  • Author(s): Ikeda Y, Tagami A, Komada M, Takahashi M
  • Journal Title: Neuroendocrinology Volume: 印刷中 Issue: 4 Pages: 357-371
  • DOI: 10.1159/000453398
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of Lis1 and DISC1 through control of Ndel1 dual-phosphorylation. (2015)
  • Author(s): 1.Okamoto, M., Iguchi, T., Hattori, T., Matsuzaki, S., Koyama, Y., Taniguchi, M., Kodama, M., Xie, M-J., Yagi, H., Shimizu, S., Konishi, Y., Yoshimi, T., Tachibana, T., Fujieda, S., Katayama, T., Ito, A., Hirotsune, S., Tohyaman, M. and Sato, M.
  • Journal Title: J Neurosci Volume: 18 Issue: 7 Pages: 2942-2958
  • DOI: 10.1523/jneurosci.5029-13.2015
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of SF-1 in neurogenesis and neuronal migration in the developing neocortex. (2015)
  • Author(s): Komada M, Takahashi M, Ikeda Y.
  • Journal Title: Neurosci Lett Volume: 600 Pages: 85-90
  • DOI: 10.1016/j.neulet.2015.06.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Filamin A-interacting protein (FILIP) is a region-specific modulator of myosin 2b and controls spine morphology and NMDA receptor accumulation. (2014)
  • Author(s): Hideshi Yagi,Takashi Nagano,Min-Jue Xie,Hiroshi Ikeda,Kazuki Kuroda,Munekazu Komada,Tokuichi Iguchi,Rahman M. Tariqur,Soichi Morikubo,Koichi Noguchi,Kazuyuki Murase,Masaru Okabe& Makoto Sato
  • Journal Title: Scientific reports Volume: 4 Issue: 1 Pages: 6353-6353
  • DOI: 10.1038/srep06353
  • Peer Reviewed / Open Access
• [Journal Article] Newborn mice exposed prenatally to bisphenol A show hyperactivity and defective neocortical development (2014)
  • Author(s): Komada M, Itoh S, Kawachi K, Kagawa N, Ikeda Y, Nagao N
  • Journal Title: Toxicology Volume: 323 Pages: 51-60
  • DOI: 10.1016/j.tox.2014.06.009
  • Peer Reviewed
• [Journal Article] Neurobehavioral evaluation of mouse newborns exposed prenatally to low-dose bisphenol A. (2014)
  • Author(s): Nagao T, Kawachi K, Kagawa N, Komada M,
  • Journal Title: J. Toxicol. Sci. Volume: 39 Pages: 234-235
  • NAID: 130004903983
  • Peer Reviewed
• [Presentation] 胎児期のエタノール曝露は大脳皮質の構造異常の原因となる脳内炎症とミクログリアの異常活性を誘発する (2017)
  • Author(s): 駒田致和、長尾哲二、池田やよい
  • Organizer: 第122回日本解剖学会総会全国学術集会
  • Place of Presentation: 長崎大学坂本キャンパス（長崎県長崎市）
  • Year and Date: 2017-03-28
• [Presentation] 胎児期エタノール曝露は大脳皮質の構造異常に因る行動異常を誘発する (2016)
  • Author(s): 駒田致和、長尾哲二、池田やよい
  • Organizer: 第58回歯科基礎医学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-08-24
• [Presentation] 胎児期のエタノール曝露は大脳皮質のミクログリアの活性異常に因る形態異常と行動異常を誘発する (2016)
  • Author(s): 駒田致和、河内宏太、井藤早紀、原奈央、長尾哲二、池田やよい
  • Organizer: 第43回日本毒性学会学術年会
  • Place of Presentation: ウインクあいち（愛知県名古屋市）
  • Year and Date: 2016-06-29
• [Presentation] 大脳皮質の発生においてSF-1は神経新生と細胞移動に関与する (2015)
  • Author(s): 駒田致和，池田やよい
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 兵庫（神戸）
  • Year and Date: 2015-07-28
• [Presentation] 胎児期のエタノール曝露は大脳皮質の形態学・行動学的異常を誘発する (2015)
  • Author(s): 駒田致和，河内宏太，井藤早紀，原奈央，長尾哲二，池田やよい
  • Organizer: 胎児期のエタノール曝露は大脳皮質の形態学・行動学的異常を誘発する
  • Place of Presentation: 神奈川（横浜）
  • Year and Date: 2015-07-25
• [Presentation] 胎児期のエタノール曝露は大脳皮質のミクログリアの活性異常に因る形態異常と行動異常を誘発する (2015)
  • Author(s): 駒田致和，河内宏太，井藤早紀，原奈央，長尾哲二，池田やよい
  • Organizer: 第42回日本毒性学会学術年会
  • Place of Presentation: 石川（金沢）
  • Year and Date: 2015-06-29
• [Presentation] Newborn mice exposed prenatally to bisphenol A show hyperactivity and defective neocortical development. (2015)
  • Author(s): 駒田致和，井藤早紀，長尾哲二，池田やよい
  • Organizer: 第120回日本解剖学会総会・全国学術集会／第92回日本生理学会大会 合同大会
  • Place of Presentation: 神戸国際会議場・展示場（神戸）
  • Year and Date: 2015-03-22
• [Presentation] 胎児期低用量ビスフェノールA曝露は発生・発達期の大脳皮質に形態・機能的異常を誘発する (2014)
  • Author(s): 駒田致和，長尾哲二，池田やよい，菅野純
  • Organizer: 第17回環境ホルモン学会研究発表会
  • Place of Presentation: 東京大学（東京）
  • Year and Date: 2014-12-09
• [Presentation] 胎児期低用量ビスフェノールA曝露による大脳皮質の発生・成熟における影響の発生毒性学的評価 (2014)
  • Author(s): 駒田致和，浅井泰子，守井見奈，松木美知枝，河内宏太，池田やよい，長尾哲二
  • Organizer: 第41回日本毒性学会学術年会
  • Place of Presentation: 神戸国際会議場・展示場（神戸）
  • Year and Date: 2014-07-02