Ethiological mechanisms of perinatal stress on lifestyle-related diseases pathogenesis

• Project/Area Number: 22591203
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Kagawa University
• Principal Investigator: MIKI Takanori 香川大学, 医学部, 准教授 (30274294)
• Co-Investigator(Kenkyū-buntansha): OHTA Kenichi 香川大学, 医学部, 助教 (50403720) ; SUZUKI Shongo 香川大学, 医学部, 助教 (50451430) ; YOKOYAMA Toshifumi 神戸大学, 農学研究科, 助教 (10380156) ; KUSAKA Takashi 香川大学, 医学部, 准教授 (50274288) ; TAKEUCHI Yoshiki 香川大学, 医学部, 教授 (20116619) ; 割田 克彦 香川大学, 医学部, 助教 (40452669)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 脳発達 / 母仔分離ストレス / 神経栄養因子 / 生活習慣病 / 脂肪組織 / エネルギー代謝 / ミトコンドリア / 肥満 / 周生期ストレス / 脳 / セロトニン / 神経栄養因子受容体 / 脂肪細胞 / UCP-1 / 代謝 / 環境-遺伝子相互作用 / DNAメチル化 / エピジェネティク

Research Abstract

This study was carried out to examine the effects of early postnatal maternal separation stress on the brain development, biological properties of adipose tissue, and the interactions between them. Wistar rats were separated from their mothers in early life. The level of various neurotrophic factor ligands/receptors in the cerebral cortex and cerebellum showed abnormal time-dependent fluctuations. Given that these factors play important roles in brain development, it can be speculated that the altered expression of these factors induced by maternal separation may interrupt normal brain development and ultimately lead to functional disruption. Furthermore, there was a significant change in the level of various mitochondrial energy-expenditure molecules. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

Research Products

• [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] Prolonged maternal separation disturbs the serotonergic system during early brain development (2014)
  • Author(s): Ohta KI, Miki T, Warita K, Suzuki S, Kusaka T, Yakura T, Liu JQ, Tamai M, Takeuchi Y
  • Journal Title: Int J Dev Neurosci Volume: 33 Issue: 1 Pages: 15-21
  • DOI: 10.1016/j.ijdevneu.2013.10.007
  • Peer Reviewed / Open Access
• [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] Differential effects of neonatal maternal separation on the expression of neurotrophic factors in rat brain. II : Regional differences in the cerebellum versus the cerebral cortex (2013)
  • Author(s): Miki T, Lee KY, Yokoyama T, Liu JQ, Kusaka T, Suzuki S, Ohta K, Warita K, Jamal M, Ueki M, Yakura T, Hosomi N, Takeuchi Y
  • Journal Title: Okajimas Folia Anat Jpn Volume: 90 Pages: 53-8
  • NAID: 130004495127
  • Peer Reviewed
• [Journal Article] Early postnatal maternal separation causes alterations in the expression ofβ3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity (2013)
  • Author(s): Miki T, Liu JQ, Ohta K, Suzuki S, Kusaka T, Warita K, Yokoyama T, Jamal M, Ueki M, Yakura T, Tamai M, Sumitani K, Hosomi N, Takeuchi Y
  • Journal Title: Biochem Biophys Res Commun Volume: 442 Issue: 1-2 Pages: 68-71
  • DOI: 10.1016/j.bbrc.2013.11.005
  • Peer Reviewed
• [Journal Article] Differential effects of neonatal maternal separation on the expression of neurotrophic factors in rat brain. II: Regional differences in the cerebellum versus the cerebral cortex. (2013)
  • Author(s): Miki T, Lee KY, Yokoyama T, Liu JQ, Kusaka T, Suzuki S, Ohta K, Warita K, Jamal M, Ueki M, Yakura T, Hosomi N, Takeuchi Y.
  • Journal Title: Okajimas Folia Anat Jpn. Volume: 90 Pages: 53-58
  • NAID: 130004495127
  • Peer Reviewed
• [Journal Article] In vitro evaluation of gene expression changes for gonadotropin-releasing hormone 1,brain-derived neurotrophic factor and neurotrophic tyrosine kinase, receptor,type 2, in response to bisphenol A treatment. (2013)
  • Author(s): Warita K, Miki T et al.
  • Journal Title: Congenit Anom (Kyoto) Volume: 53 Pages: 42-5
  • NAID: 50008814302
  • Peer Reviewed
• [Journal Article] Neonatal repetitive maternal separation causes long-lasting alterations in various neurotrophic factor expression in the cerebral cortex of rats (2012)
  • Author(s): Lee KY, Miki T, Yokoyama T, Ueki M, Warita K, Suzuki S, Ohta K, Wang ZY, Jamal M, Yakura T, Liu JQ, Hosomi N, Takeuchi Y
  • Journal Title: Life Sci Volume: 90 Pages: 578-584
  • Peer Reviewed
• [Journal Article] Neonatal repetitive maternal separation causes long-lasting alterations in various neurotrophic factor expression in the cerebral cortex of rats. (2012)
  • Author(s): Lee KY, Miki T et al.
  • Journal Title: Life Sci. Volume: 90 Issue: 15-16 Pages: 578-584
  • DOI: 10.1016/j.lfs.2012.01.021
  • Peer Reviewed
• [Journal Article] BDNF-dependent accumulation of palmitoleic acid in CNS neurons. (2012)
  • Author(s): Suzuki S, Miki Tet al.
  • Journal Title: Cell Mol Neurobiol Volume: 32 Issue: 8 Pages: 1367-73
  • DOI: 10.1007/s10571-012-9863-x
  • Peer Reviewed
• [Journal Article] Morphological evidence of an altered process of (2012)
  • Author(s): Takeuchi Y, Miki T et al.
  • Journal Title: Alcohol Alcohol Volume: 47 Issue: 6 Pages: 671-6
  • DOI: 10.1093/alcalc/ags085
  • Peer Reviewed
• [Journal Article] A high cholesterol diet given to apolipoprotein E-knockout mice has a differential effect on the various neurotrophin systems in the hippocampus (2011)
  • Author(s): Wang ZY, Miki T, et al
  • Journal Title: Metab Brain Dis Volume: 26 Issue: 3 Pages: 185-194
  • DOI: 10.1007/s11011-011-9252-z
  • Peer Reviewed
• [Journal Article] Erythropoietin attenuates isoflurane-induced neurodegeneration and learning deficits in the developing mouse brain (2011)
  • Author(s): Tsuchimoto T, Ueki M, Miki T, et al
  • Journal Title: Paediatr Anaesth Volume: 21 Issue: 12 Pages: 1209-1213
  • DOI: 10.1111/j.1460-9592.2011.03657.x
  • Peer Reviewed
• [Journal Article] Glutathione peroxidase 4 is associated with neuromelanin in substantia nigra and dystrophic axons in putamen of parkinson's brain. (2011)
  • Author(s): Bellinger FP
  • Journal Title: Mol Neurodegener. Volume: 6 Pages: 8-18
  • Peer Reviewed
• [Journal Article] Direct effects of diethylstilbestrol on the gene expression of the cholesterolside-chain cleavage enzyme(P450scc)in testicular Leydig cells. (2010)
  • Author(s): Warita K
  • Journal Title: Life Sci. Volume: 87 Pages: 281-285
  • Peer Reviewed
• [Presentation] 生後早期の母子分離ストレスが、脂肪組織エネルギー代謝関連因子に及ぼす影響 (2014)
  • Author(s): 三木崇範、太田健一、鈴木辰吾、割田克彦、日下隆、横山俊史、劉俊騫、矢倉富子、玉井求宜、竹内義喜
  • Organizer: 第119回日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医科大学キャンパス(栃木県下野市)
• [Presentation] 生後早期の母子分離ストレスが、脂肪組織エネルギー代謝関連因子に及ぼす影響 (2014)
  • Author(s): 三木崇範 太田健一 鈴木辰吾 割田克彦 日下 隆 横山俊史 劉 俊騫 矢倉富子 玉井求宣 竹内義喜
  • Organizer: 第119回日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医科大学（栃木）
• [Presentation] 幼若期の不遇な養育環境が引き起こす脳発達臨界期AMPA受容体動態の異常 (2013)
  • Author(s): 三木崇範、太田健一、鈴木辰吾、日下隆、劉俊騫、玉井求宜、矢倉富子、竹内義喜
  • 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(豊中市)
• [Presentation] 脳発達の臨界期にてらした発達障害モデルの考察-胎児性アルコール症候群を例として- (2013)
  • Author(s): 三木崇範、太田健一、鈴木辰吾、割田克彦、竹内義喜
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: サンポートホール高松・かがわ国際会議場(高松市)
• [Presentation] 幼若期の不遇な養育環境が引き起こす脳発達臨界期AMPA受容体動態の異常 (2013)
  • Author(s): 三木崇範 太田健一 鈴木辰吾 割田克彦 日下 隆 横山俊史 劉 俊騫 矢倉富子 玉井求宣 竹内義喜
  • 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] 長期間の食餌性コレステロール摂取が海馬神経栄養因子の動態に及ぼす影響 (2013)
  • Author(s): 三木崇範 太田健一 鈴木辰吾 割田克彦 日下 隆 横山俊史 劉 俊騫 矢倉富子 玉井求宣 竹内義喜
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 香川
• [Presentation] 脳発達の臨界期にてらした発達障害モデルの考察－胎児性アルコール症候群を例として－ (2013)
  • Author(s): 三木崇範 太田健一 鈴木辰吾 割田克彦 竹内義喜
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 香川
  • Invited
• [Presentation] 生後早期の母仔分離ストレスにより惹起される神経栄養因子/受容体発現レベルの変動(第2報) (2012)
  • Author(s): 三木崇範、太田健一、鈴木辰吾、割田克彦、矢倉富子、劉俊騫、竹内義喜
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学甲府キャンパス(甲府市)
• [Presentation] 母仔分離ストレスが脳発達期の海馬GluR1発現/リン酸化へ及ぼす影響 (2012)
  • Author(s): 太田健一、三木崇範、鈴木辰吾、矢倉富子、劉俊騫、玉井求宜、竹内義喜
  • Organizer: 日本解剖学会第67回中国・四国支部学術集会
  • Place of Presentation: 山口大学医学部(宇部市)
• [Presentation] 幼若期の不遇な養育環境が脳発達に与える影響-神経回路網形成に関与する因子の変化- (2012)
  • Author(s): 太田健一、三木崇範、鈴木辰吾、矢倉富子、劉俊騫、竹内義喜
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学甲府キャンパス(甲府市)
• [Presentation] 母仔分離ストレスが脳発達期の海馬GluR1発現/リン酸化へ及ぼす影響. (2012)
  • Author(s): 太田健一、三木崇範、鈴木辰吾、矢倉富子、劉俊騫、玉井求宜、竹内義喜.
  • Organizer: 日本解剖学会第67回中国・四国支部学術集会
  • Place of Presentation: 山口
  • Invited
• [Presentation] 生後早期の母仔分離ストレスにより惹起される神経栄養因子/受容体発現レベルの変動(第2報) (2012)
  • Author(s): 三木崇範, ら
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨県甲府市
• [Presentation] 生後早期の母仔分離ストレスにより惹起される小脳神経栄養因子/受容体発現レベルの変動 (2010)
  • Author(s): 三木崇範
  • Organizer: 第50回日本先天異常学会
  • Place of Presentation: 淡路夢舞台国際会議場(兵庫県)