Analysis of the relationship between the developmental disabilities in the offspring and the disturbance of the development of the brain including microglia by maternal undernutrition

• Project/Area Number: 25460242
• 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: Shiga University of Medical Science
• Principal Investigator: Udagawa Jun 滋賀医科大学, 医学部, 教授 (10284027)
• Co-Investigator(Kenkyū-buntansha): OKANO Junko 滋賀医科大学, 医学部, 准教授 (50447968) ; HAYAKAWA Takahiro 北海道大学, 医学部, 特任助教 (90415927) ; TAKEI Shiro 浜松医科大学, 医学部, 特任助教 (60398576)
• Co-Investigator(Renkei-kenkyūsha): KOJIMA Hideto 滋賀医科大学, 医学部, 教授 (00225434)
• Research Collaborator: HINO Kodai 滋賀医科大学, 大学院生 ; KIMURA Tomoko 滋賀医科大学, 医学部, 助手 (00449852) ; KANEKO Shunya 滋賀医科大学, 医学部医学科, 学生 ; HARASAWA Toshiya 滋賀医科大学, 医学部医学科, 学生 ; KONO Tadaaki 滋賀医科大学, 医学部医学科, 学生
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 胎生初期 / 低栄養ストレス / 行動異常 / 前頭前皮質 / 低栄養 / 胎生期 / リン脂質代謝

Outline of Final Research Achievements

In this study, we examined the impact of maternal undernutrition in the early pregnancy on behavior of the offspring. Maternal undernutrition led to hyperactivity and anti-anxiety-like behavior in the offspring at 8 weeks of age. The expression of the genes related to the biosynthesis of the phospholipid and the ratio of the phospholipid composition were altered in the prefrontal cortex of the undernourished group even though the level and turnover of monoamines and the distribution of the activated microglia were not changed. Recently, some studies suggest the relationship between the phospholipid and the behavior in the developmental disabilities. Taken together, alteration of the phospholipid composition in the prefrontal cortex may be one of the main causes of the abnormal behavior in the offspring, which was exposed to malnutritional stress.

Research Products

• [Journal Article] Interkinetic nuclear migration in the mouse embryonic ureteric epithelium: Possible implication for congenital anomalies of the kidney and urinary tract (2016)
  • Author(s): Motoya T, Ogawa N, Nitta T, Rafiq AM, Jahan E, Furuya M, Matsumoto A, Udagawa J, Otani H
  • Journal Title: Congenit Anom Volume: in press Issue: 3 Pages: 127-134
  • DOI: 10.1111/cga.12150
  • NAID: 130008079235
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Statistical analyses in trials for the comprehensive understanding of organogenesis and histogenesis in humans and mice (2016)
  • Author(s): Hiroki Otani, Jun Udagawa and Kanta Naito
  • Journal Title: Journal of Biochemistry Volume: 未定 Issue: 6 Pages: 553-561
  • DOI: 10.1093/jb/mvw020
  • NAID: 40020869341
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 胎児プログラミングと脳の形成 (2015)
  • Author(s): 宇田川 潤
  • Journal Title: 最新医学 Volume: 70 Pages: 875-882
• [Journal Article] Epidermis-dermis junction as a novel location for bone marrow-derived cells to reside in response to ionizing radiation (2015)
  • Author(s): Okano J, Kojima H, Katagi M, Nakae Y, Terashima T, Nakagawa T, Kurakane T, Okamoto N, Morohashi K, Maegawa H, Udagawa J
  • Journal Title: Biochemical and Biophysical Research Communications Volume: - Issue: 4 Pages: 695-701
  • DOI: 10.1016/j.bbrc.2015.04.094
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats (2015)
  • Author(s): Fujiyama F, Nakano T, Matsuda W, Furuta T, Udagawa J, Kaneko T
  • Journal Title: Brain Struct. Funct. Volume: published online Issue: 9 Pages: 1-8
  • DOI: 10.1007/s00429-015-1152-2
  • Peer Reviewed / Open Access
• [Journal Article] Effect of prolactin-induced protein on human skin: new insight into the digestive action of this aspartic peptidase on the stratum corneum and its induction of keratinocyte proliferation. (2015)
  • Author(s): Sugiura S, Tazuke M, Ueno S, Sugiura Y, Kato I, Miyahira Y, Yamamoto Y, Sato H, Udagawa J, Uehara M, Sugiura H
  • Journal Title: J Invest Dermatol Volume: 135 Issue: 3 Pages: 776-785
  • DOI: 10.1038/jid.2014.448
  • Peer Reviewed
• [Journal Article] Fetal jaw movement affects Ihh signaling in mandibular condylar cartilage development: The possible role of Ihh as mechanotransduction mediator (2014)
  • Author(s): Jahan E, Matsumoto A, Rafiq AM, Hashimoto R, Inoue T, Udagawa J, Sekine J, Otani H
  • Journal Title: Archives of Oral Biology Volume: 59 Issue: 10 Pages: 1108-1118
  • DOI: 10.1016/j.archoralbio.2014.06.009
  • Peer Reviewed / Open Access
• [Journal Article] Statistical analysis with dilatation for development process of human fetuses (2014)
  • Author(s): Naito K, Notsu A, Udagawa J, Otani H
  • Journal Title: Stat Methods Med Res Volume: - Issue: 1 Pages: 176-200
  • DOI: 10.1177/0962280214543405
  • Peer Reviewed
• [Journal Article] Hyperglycemia induces abnormal gene expression in hematopoietic stem cells and their progeny in diabetic neuropathy. (2014)
  • Author(s): Katagi M, Terashima T, Okano J, Urabe H, Nakae Y, Ogawa N, Udagawa J, Maegawa H, Matsumura K, Chan L, Kojima H
  • Journal Title: FEBS letters. Volume: 588 Issue: 6 Pages: 1080-1086
  • DOI: 10.1016/j.febslet.2014.02.030
  • Peer Reviewed
• [Journal Article] The roles of retinoic acid signaling in normal and abnormal development of the palate (2014)
  • Author(s): Okano J, Udagawa J, Shiota K
  • Journal Title: Congenital Anomalies Volume: 印刷中 Issue: 2 Pages: 69-76
  • DOI: 10.1111/cga.12049
  • Peer Reviewed
• [Presentation] 胎生期低栄養暴露による生後の脳内リン脂質代謝の変化と行動異常 (2016)
  • Author(s): 日野広大、金子隼也、木村智子、武井史郎、杉原洋行、瀬藤光利、小島秀人、宇田川潤
  • Organizer: 第121回日本解剖学会総会・学術集会
  • Place of Presentation: 郡山市
  • Year and Date: 2016-03-28
• [Presentation] 間葉系幹細胞の低栄養ストレスは生後における後肢骨の成長を抑制する (2016)
  • Author(s): 木村智子、日野広大、醍醐弥太郎、高瀬隆太、日野信次朗、中尾光善、宇田川潤
  • Organizer: 第121回日本解剖学会総会・学術集会
  • Place of Presentation: 郡山市
  • Year and Date: 2016-03-28
• [Presentation] Interkinetic nuclear migration in the developing endoderm- and mesoderm-origin epithelial tubular structures (2016)
  • Author(s): Otani H, Motoya T, Ogawa N, Nitta T, Rafiq AM, Jahan E, Keneda R, Furuya M, Matsumoto A, Udagawa J, Hatta T
  • Organizer: 第121回日本解剖学会総会・学術集会
  • Place of Presentation: 郡山市
  • Year and Date: 2016-03-28
• [Presentation] 低栄養暴露直後の神経幹細胞の遺伝発現変化と生後の行動異常 (2015)
  • Author(s): 日野広大、金子隼也、木村智子、原澤俊也、河野匡暁、高野淳、醍醐弥太郎、小島秀人、島田ひろき、石垣靖人、八田稔久、竹内成子、遠山育夫、山田尚登、宇田川潤
  • Organizer: 第4回日本DOHaD研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-08-01
• [Presentation] 胎生初期の低栄養暴露は生後における後肢骨成長を抑制する (2015)
  • Author(s): 木村智子、日野広大、河野匡暁、金子隼也、原澤俊也、玉川俊広、森田航、中務真人、醍醐弥太郎、高野淳、新田哲久、牛尾哲敏、宇田川潤、工藤基
  • Organizer: 第55回日本先天異常学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-07-25
• [Presentation] kAPラットにおける網膜幹細胞・前駆細胞の急速な消失現象 (2015)
  • Author(s): 日野広大、岩本壮太郎、川野純一、高野淳、醍醐弥太郎、宇田川潤
  • Organizer: 第55回日本先天異常学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-07-25
• [Presentation] Cutaneous retinoid acid levels determine hair follicle development and down-growth (2015)
  • Author(s): 岡野純子、Yasupa Stuart、坂井靖夫、Morasso Maria、宇田川潤
  • Organizer: 第55回日本先天異常学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-07-25
• [Presentation] 器官形成期マウス胚の気管・食道上皮におけるinterkinetic nuclear migrationの解析 (2015)
  • Author(s): 兼田稜、橋本龍樹、荒内亮輔、古屋智英、佐藤文夫、宇田川潤、大谷浩
  • Organizer: 第55回日本先天異常学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-07-25
• [Presentation] マウス尿管の発生過程におけるInterkinetic nuclear migrationおよびConvergent extensionの解析 (2015)
  • Author(s): 元矢知志、新田哲哉、Rafiq Ashiq、Jahan Esrat、小川典子、古屋智英、松本暁洋、宇田川潤、大谷浩
  • Organizer: 第55回日本先天異常学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-07-25
• [Presentation] 胎生期ストレスと脳の発生異常 (2015)
  • Author(s): 宇田川潤
  • Organizer: 第85回日本衛生学会学術集会自由集会
  • Place of Presentation: 和歌山市
  • Year and Date: 2015-03-26
• [Presentation] Programmed cell death in the developing optic cup in anophthalmia mutant (kAP)-rat. (2015)
  • Author(s): Hino K, Iwamoto S, Takano A, Kawano J, Daigo Y, Udagawa J
  • Organizer: 第120回日本解剖学会総会・全国学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-22
• [Presentation] Postnatal growth of hindlimb bones are restricted by undernutrition during early embryonic period. (2015)
  • Author(s): Kimura T, Hino K, Kono T, Kaneko S, Tamagawa T, Morita W, Nakatsukasa M, Daigo Y, Takano A, Nitta N, Ushio N, Udagawa J, Kudo M
  • Organizer: 第120回日本解剖学会総会・全国学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-22
• [Presentation] Interkinetic nuclear migration in the mouse embryonic ureteric epithelium. (2015)
  • Author(s): Motoya T, Ogawa N, NittaT, Rafiq AM, Esrat J, Furuya M, Matsumoto A, Udagawa J, Otani H.
  • Organizer: 第120回日本解剖学会総会・全国学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-22
• [Presentation] The progeny of bone marrow stem cells with metabolic memory perturbs skin homeostasis. (2015)
  • Author(s): Okamoto N, Okano J, Kojima H, Katagi M, Nakae Y, Terashima T, Udagawa J
  • Organizer: 第120回日本解剖学会総会・全国学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-21
• [Presentation] Circadian rhythm in skin. (2015)
  • Author(s): Morohashi K, Okano J, Kojima H, Terashima T, Katagi M, Nakae Y, Udagawa J
  • Organizer: 第120回日本解剖学会総会・全国学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-03-21
• [Presentation] Exposure to malnutrition in early pregnancy leads to hyperactivity in rat offspring. (2014)
  • Author(s): Kaneko S, Harasawa T, Kono T, Kimura T, Hino K, Kubo Y, Takano A, Daigo Y, Kojima H, Shimada H, Ishigaki Y, Hatta T, Takeuchi S, Kanai H, Tooyama I, Yamada N, Udagawa J
  • Organizer: NeuroScience 2014
  • Place of Presentation: ワシントンDC，アメリカ合衆国
  • Year and Date: 2014-11-17
• [Presentation] ImageJによる定量的および立体的な組織画像解析 (2014)
  • Author(s): 宇田川潤
  • Organizer: 第39回組織細胞化学講習会
  • Place of Presentation: 大津市
  • Year and Date: 2014-08-06
• [Presentation] 胎生初期低栄養暴露による体格形成変化に ついての解析 (2014)
  • Author(s): 木村智子、日野広大 河野匡暁、金子隼也 原澤俊也、玉川俊広、森田航、中務真人、醍醐弥太郎、高野淳、新田哲久、牛尾哲敏、宇田川潤、工藤基
  • Organizer: 第54回日本先天異常学会学術集会
  • Place of Presentation: 相模原市
  • Year and Date: 2014-07-26
• [Presentation] 胎生初期低栄養暴露による生後の後肢骨成長変化についての解析 (2014)
  • Author(s): 木村智子、玉川俊宏、金子隼也、原澤俊也、河野匡暁、日野広大、森田航、中務真人、山田重人、宇田川潤、工藤基
  • Organizer: 第119回日本解剖学会総会・学術集会
  • Place of Presentation: 自治医科大学、下野市
• [Presentation] Arg-Gly-Asp（RGD）配列/インテグリンα5β1シグナルの軟骨内骨化への関与のin vivo解析 (2014)
  • Author(s): 井上隆之、橋本龍樹、松本暁洋、Jahan Esrat、Rafiq Ashiq、宇田川潤、八田稔久、大谷浩
  • Organizer: 第119回日本解剖学会総会・学術集会
  • Place of Presentation: 自治医科大学、下野市
• [Presentation] 胎生期における眼杯と水晶体の消失過程の解析 (2014)
  • Author(s): 日野広大，瀧公介，原澤俊也，岩本壮太郎，川野純一，工藤基，宇田川潤
  • Organizer: 第119回日本解剖学会総会・学術集会
  • Place of Presentation: 自治医科大学、下野市
• [Presentation] X-ray irradiation induces immigration of bone marrow cells into epidermis. (2014)
  • Author(s): 岡野純子、小島秀人、樫美和子、中江由希、寺島智也、小川暢弘、浦部博志、宇田川潤
  • Organizer: 第119回日本解剖学会総会・学術集会
  • Place of Presentation: 自治医科大学、下野市
• [Presentation] 妊娠初期の母体低栄養による出生仔の後肢成長変化についての形態学的解析 (2013)
  • Author(s): 木村智子、玉川俊広、金子隼也、原澤俊也、河野匡暁、日野広大、野津瑛未奈、森田航、中務真人、山田重人、宇田川潤、工藤基
  • Organizer: 第2回日本DOHaD研究会学術集会
  • Place of Presentation: 厚生労働省戸山研究庁舎、東京
• [Presentation] 子宮外発生法を用いた軟骨内骨化メカニズムのin vivo解析 (2013)
  • Author(s): 井上隆之、橋本龍樹、松本暁洋、Jahan Esrat、Rafiq Ashiq、宇田川潤、八田稔久、大谷浩
  • Organizer: 第53回日本先天異常学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター、大阪
• [Presentation] 子宮内環境と精神疾患および発達障害－動物実験を中心に－ (2013)
  • Author(s): 宇田川 潤
  • Organizer: 第53回日本先天異常学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター、大阪
• [Presentation] 胎生期の低栄養により多動を生じる仔ラットの脳の解析 (2013)
  • Author(s): 河野匡暁、金子隼也、原澤俊也、野津瑛未奈、田中邦和、小島秀人、金井裕彦、竹内成子、木村智子、遠山育夫、八田稔久、山田尚登、村上哲男、岡野純子、宇田川潤
  • Organizer: 第53回日本先天異常学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター、大阪
• [Presentation] 胎生初期の低栄養が仔ラットの骨成長に及ぼす影響 (2013)
  • Author(s): 木村智子、玉川俊宏、金子隼也、原澤俊也、河野匡暁、野津瑛未奈、森田航、中務真人、山田重人、宇田川潤、工藤基
  • Organizer: 第53回日本先天異常学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター、大阪
• [Presentation] 骨髄移植に際して必要な放射線照射が表皮組織に与える影響
  • Author(s): 岡野純子、小島秀人、樫美和子、中江由希、寺島智也、小川暢弘、浦部博志、宇田川潤
  • Organizer: 第89回日本解剖学会近畿支部学術集会
  • Place of Presentation: 奈良先端科学技術大学院大学、生駒市