胎児期における脳内環境の破綻と育児放棄の発症機序の解明

• Project Area: Brain Environment
• Project/Area Number: 24111506
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Gunma University
• Principal Investigator: 下川 哲昭 群馬大学, 医学(系)研究科(研究院), 准教授 (90235680)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: CIN85 / 脳内環境 / 育児放棄 / ドーパミン / プロラクチン / 哺育行動 / ドパミン / 胎児期脳内環境 / 国際情報交換 / ドイツ / ノルウェー

Research Abstract

1. 育児放棄における細胞外環境膜の影響
受容体のダウンレギュレーションを制御するCIN85を欠損したマウス (CIN85 KO) は育仔放棄をする。この原因は、CIN85 KOの胎児期のプロラクチン(PRL) 曝露の不足であると考え、妊娠中のCIN85 KOにPRL投与を行ったところ、得られた仔達は数ヶ月後、仔育て行動と仔の生育数が顕著に上昇した。現在、CIN85 KO由来の受精卵を野生型マウス (WT、正常なPRL濃度である)へ移植し、逆にWTの受精卵をCIN85 KO（低PRL濃度である）へ移植後、得られた仔達の仔育て行動と仔の生育数を解析する実験を推進している。
2. 甲状腺ホルモン機能低下によるドパミン軸索輸送の障害
胎児期から新生児期にかけての中枢神経系の発達や機能は甲状腺ホルモンに依存している。先天性甲状腺機能低下症ラット(rdw rat)は、協調運動の低下と低運動性 (hypoactivity)を示した。協調運動の低下は小脳プルキンエ細胞の発達障害によるものであり、hypoactivityは甲状腺ホルモン欠乏がneuronal tubulinの合成低下を招き、黒質-線条体におけるドーパミン分子の軸索輸送を障害していることが原因であることが解った。

Current Status of Research Progress

Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Altered cerebellum development and dopamine distribution in a rat genetic model with congenital hypothyroidism. (2014)
  • Author(s): Shimokawa N, Yousefi B, Morioka S, Yamaguchi S, Ohsawa A, Hayashi H, Azuma A, Mizuno H, Kasagi M, Masuda H, Jingu H, Furudate SI, Haijima A, Takatsuru Y, Iwasaki T, Umezu M, Koibuchi N.
  • Journal Title: J Neuroendocrinol. Volume: 26 Issue: 3 Pages: 164-175
  • DOI: 10.1111/jne.12135
  • Peer Reviewed / Open Access
• [Journal Article] Possible involvement of IGF-1 signaling on compensatory growth of the infraspinatus muscle induced by the supraspinatus tendon detachment of rat shoulder (2014)
  • Author(s): Ichinose T, Lesmana R, Yamamoto A, Kobayashi T, Shitara H, Shimoyama D, Takatsuru Y, Iwasaki T, Shimokawa N, Takagishi K, Koibuchi N
  • Journal Title: Physiological Rep Volume: 2 Issue: 1 Pages: 1-10
  • DOI: 10.1002/phy2.197
  • Peer Reviewed / Open Access
• [Journal Article] The effect of low dose lipopolysaccharide on thyroid hormone-regulated actin cytoskeleton modulation and type 2 iodothyronine deiodinase activity in astrocytes. (2013)
  • Author(s): Xu M, Iwasaki T, Shimokawa N, Sajdel-Sulkowska EM, Koibuchi N.
  • Journal Title: Endocrine journal Volume: 60 Pages: 1221-1230
  • NAID: 130004770400
  • Peer Reviewed
• [Journal Article] Critical role of the astrocyte for functional remodeling in contralateral hemisphere of somatosensory cortex after stroke. (2013)
  • Author(s): Takatsuru Y, Eto K, Kaneko R, Masuda H, Shimokawa N, Koibuchi N, Nabekura J.
  • Journal Title: Journal of neurosciences Volume: 33 Pages: 4683-4692
  • Peer Reviewed
• [Journal Article] Effects of perinatal lipopolysaccharide (LPS) exposure on the developing rat brain; modeling the effect of maternal infection on the developing human CNS. (2013)
  • Author(s): Xu M, Sulkowski ZL, Parekh P, Khan A, Chen T, Midha S, Iwasaki T, Shimokawa N, Koibuchi N, Zavacki AM, Sajdel-Sulkowska EM.
  • Journal Title: Cerebellum Volume: 12 Issue: 4 Pages: 572-586
  • DOI: 10.1007/s12311-013-0465-z
  • Peer Reviewed
• [Journal Article] Interaction of silencing mediator for retinoid and thyroid receptors with steroid and xenobiotic receptor on multidrug resistance 1 promoter (2013)
  • Author(s): Kazumi Hirooka-Masui
  • Journal Title: Life Sciences Volume: 92 Issue: 17-19 Pages: 911-915
  • DOI: 10.1016/j.lfs.2013.03.007
  • Peer Reviewed
• [Journal Article] Critical role of the astrocyte for functional remodeling in contralateral hemisphere of somatosensory cortex after stroke. (2013)
  • Author(s): Takatsuru Y, Eto K, Kaneko R, Masuda H, Shimokawa N, Koibuchi N, Nabekura J.
  • Journal Title: J Neurosci. Volume: 33 Issue: 11 Pages: 4683-4692
  • DOI: 10.1523/jneurosci.2657-12.2013
  • Peer Reviewed
• [Journal Article] CIN85 is a critical mediator in the regulation of behavior and metabolism. (2013)
  • Author(s): Shimokawa N.
  • Journal Title: Biomedical reports Volume: 4 Pages: 59-65
  • Peer Reviewed
• [Journal Article] Effects of Perinatal Lipopolysaccharide (LPS) Exposure on the Developing Rat Brain; Modeling the Effect of Maternal Infection on the Developing Human CNS. (2013)
  • Author(s): Xu M, Sulkowski ZL, Parekh P, Khan A, Chen T, Midha S, Iwasaki T, Shimokawa N, Koibuchi N, Zavacki AM, Sajdel-Sulkowska EM.
  • Journal Title: Cerebellum Volume: 12 Pages: 206-213
  • Peer Reviewed
• [Journal Article] Alterations of biochemical marker levels and myonuclear numbers in rat skeletal muscle after ischemia-reperfusion. (2012)
  • Author(s): Itoh M
  • Journal Title: Mol Cell Biochem. Volume: 373 Issue: 1-2 Pages: 11-18
  • DOI: 10.1007/s11010-012-1470-0
  • Peer Reviewed
• [Journal Article] Lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) causes hyperactivity in male rat pups by aberrant increase in dopamine and its receptor. (2012)
  • Author(s): Lesmana R
  • Journal Title: Environ Toxicol. Volume: Epub ahead of print Issue: 8 Pages: 9-16
  • DOI: 10.1002/tox.21815
  • Peer Reviewed
• [Presentation] Impairment of rearing behaviors in CIN85-deficient mice. (2013)
  • Author(s): 下川 哲昭、池澤 淳、増田 真之佑、鯉淵 典之
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-27
• [Presentation] 先天性甲状腺機能低下症(rdw)ラットの小脳機能に対するチロキシン経口投与の効果 (2013)
  • Author(s): 林 秀華、東 杏莉、水野 寛之、増田 真之佑、于 #29840;、レスマナ ロニー、蓜島 旭、高鶴 裕介、 岩崎 俊晴、下川 哲昭、梅津 元昭、鯉淵 典之
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-27
• [Presentation] CIN85欠損における胎仔期脳内環境の破綻と育仔放棄 (2013)
  • Author(s): 下川 哲昭、池澤 淳、増田 真之佑、鯉淵 典之
  • Organizer: 第8回環境生理学プレコングレス
  • Place of Presentation: 東京
  • Year and Date: 2013-03-26
• [Presentation] Impairment of maternal behaviour by lack of CIN85. (2013)
  • Author(s): Shimokawa N, Ikezawa J, Masuda S, Koibuchi N.
  • Organizer: FENS Featured Regional Meeting
  • Place of Presentation: Prague, Czech Republic
• [Presentation] Decision mechanisms to child-rearing in fetal period. (2013)
  • Author(s): Shimokawa N.
  • Organizer: International Symposium on Prediction and Dicision Making 2013
  • Place of Presentation: Kyoto, Japan
• [Presentation] The cerebral glucose transporter SLC45A1 is mutated in individuals with non-syndromic intellectual disability and epilepsy. (2013)
  • Author(s): Srour M, Shimokawa N, Hamdan FF, Dobrzeniecka S, Rouleau GA, Poulin C, Michaud JL.
  • Organizer: American Society of Human Genitics 2013
  • Place of Presentation: Boston, MA, USA
• [Presentation] Aerobic training influences plasma concentration of thyroid hormone and potentiates thyroid hormone responsiveness to several genes in rat skeletal muscle. (2012)
  • Author(s): Lesmana R., Iwasaki T., Shimokawa N., Koibuchi N.
  • Organizer: 10th Asia and Oceania Thyroid Association Congress
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2012-10-21
• [Presentation] Lack of CIN85 in brain causes impared maternal behaviors by aberrant dopamine-prolactin signaling. (2012)
  • Author(s): Shimokawa N, Ikezawa J, Haglund K, Koibuchi N, Dikic I.
  • Organizer: The 4th EMBO meeting
  • Place of Presentation: Nice, France
  • Year and Date: 2012-09-22
• [Presentation] CIN85の機能欠損による行動異常の解析 (2012)
  • Author(s): 下川 哲昭、池澤 淳、鯉淵 典之
  • Organizer: 平成24年度日本生化学会関東支部例会
  • Place of Presentation: 前橋、群馬
  • Year and Date: 2012-06-23
• [Presentation] 脳内環境の破綻と神経・精神異常の発症メカニズムの解析 ―「多動症」や「育児放棄」への一考察 ―
  • Author(s): 下川哲昭
  • Organizer: 世界脳週間2013
  • Place of Presentation: 前橋、群馬
  • Invited
• [Remarks] 群馬大学医学系研究科 応用生理学分野
  • URL: http://nori3.dept.med.gunma-u.ac.jp/