Regulation of energy metabolism between brain and periferal organs; molecular mechanism of stress-induced life style-related diseases

• Project/Area Number: 26461636
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Kagawa University
• Principal Investigator: MIKI TAKANORI 香川大学, 医学部, 教授 (30274294)
• Co-Investigator(Kenkyū-buntansha): 太田 健一 香川大学, 医学部, 助教 (50403720) ; 鈴木 辰吾 香川大学, 医学部, 講師 (50451430) ; 割田 克彦 鳥取大学, 農学部, 准教授 (40452669) ; 横山 俊史 神戸大学, 農学研究科, 助教 (10380156) ; 日下 隆 香川大学, 医学部, 教授 (50274288)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ストレス / 脳発達 / 生活習慣病 / 肥満 / エネルギー代謝 / 末梢臓器 / 腸内細菌叢 / 母仔分離 / 視床下部 / BDNF / TrkB / 母子分離 / 代謝関連臓器 / コレステロール / コルチコステロン / 神経回路網形成 / 末梢臓器関連

Outline of Final Research Achievements

This study was carried out to examine the effects of early postnatal maternal separation stress on the developmental crosstalk between the brain and peripheral energy-related organs. Our study can obtain insight understanding etiological mechanisms of life style-related diseases, such as obesity.　Maternally separated rats showed abnormal alterations in neurotrophic factor expressions, their signal transduction systems and synapse structure protein phosphorylations. Furthermore, maternal separation stress affected various enzymes that involves in lipid metabolism. Examination on gut microbiota in these animals showed a disturbance in microbial composition leading to cause abnormal metabolism and/or nutrition. Our study showed that maternal separation stress during early postnatal life can affect the functions of both brain and peripheral organs that causes obesity in later life.

Research Products

• [Journal Article] 神経毒とNeuroscience エタノール (2017)
  • Author(s): 三木崇範 太田健一 鈴木辰吾
  • Journal Title: Clinical Neuroscience Volume: 35 Pages: 1393-1397
• [Journal Article] Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development. (2017)
  • Author(s): Ohta KI, Suzuki S, Warita K, Kaji T, Kusaka T, Miki T.
  • Journal Title: J Neurochem. Volume: 141 Issue: 2 Pages: 179-194
  • DOI: 10.1111/jnc.13977
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional interaction between BDNF and mGluR II in vitro: BDNF down-regulated mGluR II gene expression and an mGluR II agonist enhanced BDNF-induced BDNF gene expression in rat cerebral cortical neurons (2017)
  • Author(s): Suzukia S, Koshimizu H, Adachi N, Matsuoka H, Fushimi S, Ono J, Ohta K, Mikia T.
  • Journal Title: Peptides Volume: 21 Pages: 42-49
  • DOI: 10.1016/j.peptides.2017.01.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ethanol and acetaldehyde differentially alter extracellular dopamine (2016)
  • Author(s): Jamal M, Ameno K, Miki T, Tanaka N, Ito A, Ono J, Takakura A, Kumihashi M, Kinoshita H.
  • Journal Title: Neurotoxicology. Volume: 52 Pages: 204-209
  • DOI: 10.1016/j.neuro.2015.12.011
  • Peer Reviewed / Open Access
• [Journal Article] Cerebral blood volume measurement using near-infrared time-resolved spectroscopy and histopathological evaluation after hypoxic-ischemic insult in newborn piglets. (2015)
  • Author(s): Nakamura M, Jinnai W, Hamano S, Nakamura S, Koyano K, Chiba Y, Kanenishi K, Yasuda S, Ueno M, Miki T, Hata T, Kusaka T.
  • Journal Title: International Journal of Developmental Neuroscience Volume: 42 Issue: 1 Pages: 1-9
  • DOI: 10.1016/j.ijdevneu.2015.02.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Early postnatal repeated maternal deprivation causes a transient increase in OMgp and BDNF in rat cerebellum suggesting precocious myelination (2014)
  • Author(s): Miki T, Yokoyama T, Kusaka T, Suzuki S, Ohta K, Warita K, Wang ZY, Sumitani K, Bellinger FP, Tamai M, Liu JQ, Yakura T, Takeuchi Y
  • Journal Title: J Neurol Sci, J Neurol Sci Volume: 336 Issue: 1-2 Pages: 62-7
  • DOI: 10.1016/j.jns.2013.10.007
  • Peer Reviewed / Open Access
• [Journal Article] Development of an artificial calcium-dependent transcription factor to detect sustained intracellular calcium elevation. (2014)
  • Author(s): Suzuki S, Murotomi K, Nakajima Y, Kawai K, Ohta K, Warita K, Miki T, and Takeuchi Y.
  • Journal Title: ACS synthetic biology Volume: 17 Issue: 10 Pages: 717-722
  • DOI: 10.1021/sb500070c
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Short-term ethanol exposure causes imbalanced neurotrophic factor allocation in the basal forebrain cholinergic system: a novel insight into understanding the initial processes of alcohol addiction. (2014)
  • Author(s): Miki T, Kusaka T, Yokoyama T, Ohta K, Suzuki S, Warita K, Jamal M, Wang ZY, Ueki M, Liu JQ, Yakura T, Tamai M, Sumitani K, Hosomi N, Takeuchi Y.
  • Journal Title: J Neural Transm. Volume: 121 Issue: 2 Pages: 201-210
  • DOI: 10.1007/s00702-013-1085-y
  • Peer Reviewed / Open Access
• [Journal Article] A unique pattern of bisphenol a effects on nerve growth factor gene expression in embryonic mouse hypothalamic cell line N-44. (2014)
  • Author(s): Warita K, Mitsuhashi T, Hoshi N, Ohta K, Suzuki S, Takeuchi Y, Miki T
  • Journal Title: Arh Hig Rada Toksikol Volume: 65 Issue: 3 Pages: 293-299
  • DOI: 10.2478/10004-1254-65-2014-2494
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 母子分離が破綻させる内側前頭前皮質の興奮/抑制バランス (2018)
  • Author(s): 小澤 徹、太田健一、鈴木辰吾、三木崇範
  • Organizer: 第123回日本解剖学会総会・全国学術集会
• [Presentation] 脳発達期の母子分離による扁桃体の興奮/抑制バランス崩壊. (2017)
  • Author(s): 太田 健一、 鈴木 辰吾、天雲 千晶、日下 隆、三木 崇範.
  • Organizer: 第122回日本解剖学会総会・全国学術集会
  • Place of Presentation: 長崎県
  • Year and Date: 2017-03-28
• [Presentation] 脳発達早期の母子分離は海馬CA1領域におけるBDNF-ERKシグナルと樹状突起スパイン形成に影響を与える (2016)
  • Author(s): 太田健一、鈴木辰吾、日下 隆、三木崇範
  • Organizer: 第5回日本DOHaD学会
  • Place of Presentation: 東京都
  • Year and Date: 2016-07-23
• [Presentation] 脳発達期の母仔分離による海馬興奮性シナプス形成異常 (2015)
  • Author(s): 加地智洋、太田健一、鈴木辰吾、三木崇範
  • Organizer: 日本解剖学会 第70階中国・四国支部学術集会
  • Place of Presentation: 愛媛大学 城北キャンパス
  • Year and Date: 2015-10-24
• [Presentation] 養育環境が脳をかえる：分子～症状を双方向に見通す (2015)
  • Author(s): 三木崇範、太田健一、鈴木辰吾
  • Organizer: 日本赤ちゃん学会 第15回学術集会
  • Place of Presentation: 香川 サンポート香川 国際会議場
  • Year and Date: 2015-06-28
  • Invited
• [Presentation] 脳発達早期のストレスは海馬におけるBDNF 発現とその関連因子を低下させる (2015)
  • Author(s): 太田健一、鈴木辰吾、割田克彦、日下隆、三木崇範
  • 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
  • Year and Date: 2015-03-21 – 2015-03-23