Cytoarchitectural changes of brain induced by alcohol exposure : effects on Notch signal pathway

2009 Fiscal Year Final Research Report

• Project/Area Number: 18591292
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kagawa University
• Principal Investigator: TAKEUCHI Yoshiki Kagawa University, 医学部, 教授 (20116619)
• Co-Investigator(Kenkyū-buntansha): MIKI Takanori 香川大学, 医学部, 准教授 (30274294) ; MATSUMOTO Yoshiki 香川大学, 医学部, 助教 (90335844) ; WARITA Katsuhiko 香川大学, 医学部, 助教 (40452669) ; NAKAMURA Kazuhiko 浜松医科大学, 医学部附属病院, 講師 (80263911) ; IMAGAWA Tomohiro 鳥取大学, 農学部, 准教授 (20232605) ; YOKOYAMA Toshifumi 神戸大学, 農学部, 助教 (10380156)
• Project Period (FY): 2006 – 2009
• Keywords: アルコール / ノッチシグナル / 遺伝子発現 / 脳組織 / 神経機能 / 精神障害

Research Abstract

Notch signaling, related with maintenance of Stemness in culture, is well known to play an important role in neuroprotective and proliferative properties. Therefore, alcohol exposure showed to activate the Notch pathway. As results, Notch signaling related receptors, such as Platelet-derived growth factor (PDGF), Brain-derived neurotrophic factor (BDNF) and Nerve growth factor (NGF), were indicated to be strongly expressed. However, there are significant lacunae about formation of neuronal network under expression of these receptors. Particularly, changes of neuronal membranes, axonal transport and synaptic transmission should be studied. In this point, a study of synaptic transport of protein might provide biological solution for psychiatric disorder of alcoholism.

Research Products

• [Journal Article] Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population (2010)
  • Author(s): Kushima I, Aleksic B, Ito Y, Nakamura Y, Nakamura K, (他11名)
  • Journal Title: J Hum Genet. 55 Pages: 133-136
  • Peer Reviewed
• [Journal Article] Decreased serum levels of adiponectin in subjects with autism (2010)
  • Author(s): Fujita-Shimizu A, Suzuki K, Nakamura K, (他15名)
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry. 34 Pages: 455-458
  • Peer Reviewed
• [Journal Article] Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association studies in autism and schizophrenia in Japanese subjects. (2010)
  • Author(s): Maekawa M, Iwayama Y, Arai R, Nakamura K, (他8名)
  • Journal Title: J Hum Genet. 55(2) Pages: 127-30
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• [Journal Article] Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. (2010)
  • Author(s): Nakamura K, Sekine Y, Ouchi Y, (他12名)
  • Journal Title: Arch Gen Psychiatry. 67(1) Pages: 59-68
  • Peer Reviewed
• [Journal Article] Effects of short-term ethanol ingestion on the expression of neurotrophins and their receptors: No changes in the expression of the glial-derived neurotrophic factor in the mouse hippocampus (2010)
  • Author(s): Ueno T, Miki T, Wang ZY, Yokoyama T, Lee KY, Kusaka T, Warita K, Sumitani K, Matsumoto Y, Yakura T, Liu JQ, Bedi KS, Takeuchi Y.
  • Journal Title: Current Neurobiol. 1 Pages: 40-45
  • Peer Reviewed
• [Journal Article] Takeuch Y GABA expression in c-Fos immunoreactive neurons of the rat periaqueductal gray induced by electroacupuncture at the point of Zusanli. (2010)
  • Author(s): Fusumada K, Yokoyama T, Miki T, Matsumoto Y, Warita K, Wang ZY, Yakura T, Liu JQ
  • Journal Title: Current Neurobiol. 1 Pages: 10-13
  • Peer Reviewed
• [Journal Article] Short-term exposure to ethanol causes a differential response between nerve growth factor and brain-derived neurotrophic factor ligand/receptor systems in the mouse cerebellum (2010)
  • Author(s): Wang ZY, Miki T, Lee KY, Yokoyama T, Kusaka T, Sumitani K, Warita K, Matsumoto Y, Yakura T, Hosomi N, Ameno K, Bedi KS, Takeuchi Y
  • Journal Title: Neuroscience 165 Pages: 485-491
  • Peer Reviewed
• [Journal Article] Brain Serotonin and Dopamine Transporter Bindings in Adults with High-Functioning Autism (2010)
  • Author(s): Nakamura K, Sekine Y, (他14名)
  • Journal Title: Arch Gen Psychiatry. 67(1) Pages: 59-68
  • Peer Reviewed
• [Journal Article] An association study of monoamine oxidase A (MAOA) gene polymorphism in methamphetamine psychosis (2009)
  • Author(s): Nakamura K, Sekine Y, (他14名)
  • Journal Title: Neurosci Lett 455 Pages: 120-123
  • Peer Reviewed
• [Journal Article] Mitochondrial DNA haplogroup analysis in patients with bipolar disorder (2009)
  • Author(s): Kazuno AA, Munakata K, Mori K, Nanko S, Kunugi H, Nakamura K, (他5名)
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet 150B Pages: 243-247
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• [Journal Article] Early postnatal ethanol exposure induces fluctuation in the expression of BDNF mRNA in the developing rat hippocampus. (2008)
  • Author(s): Miki T, Kuma H, Yokoyama T, Sumitani K, Matsumoto Y, Kusaka T, Warita K, Wang ZY, Hosomi N, Imagawa T, Bedi KS, Itoh S, Nakamura Y, Takeuchi Y
  • Journal Title: Acta Neurobiol Exp 68 Pages: 484-493
  • Peer Reviewed
• [Journal Article] Ethanol neurotoxicity and dentate gyrus development (2008)
  • Author(s): Miki T, Yokoyama T, Sumitani K, Kusaka T, Warita Y, Matsumoto Y, Wang ZY, Wilce PA, Bedi KS, Itoh, S, Takeuchi Y
  • Journal Title: Congenital Anomalies 48 Pages: 110-117
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• [Journal Article] Characterization of neuroprogenitor cells expressing the PDGF beta-receptor within the subventricular zone of postnatal mice (2008)
  • Author(s): Ishii Y, Matsumoto Y, Watanabe R, Elmi M, Fujimori T, Nissen J, Cao Y, Nabeshima YI, Sasahara M, Funa K
  • Journal Title: Mol Cell Neurosci 37 Pages: 507-518
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• [Journal Article] Activin A and Equine Chorionic Gonadotropin Recover Reproductive Dysfunction Induced by Neonatal Exposure to an Estrogenic Endocrine Disruptor in Adult Male Mice (2008)
  • Author(s): Warita K, Okamoto K, Mutoh KI, Hasegawa Y, Yue ZP, Yokoyama T, Matsumoto Y, Miki T, Takeuchi Y, Kitagawa H, Sugawara T, Hoshi N
  • Journal Title: Biol Reprod 78 Pages: 59-67
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• [Journal Article] Genetic and expression analyses reveal elevated expression of syntaxin 1A (STX1A) in high functioning autism. (2008)
  • Author(s): Nakamura K, Anitha A, (他18名)
  • Journal Title: Int J Neuropsychopharmacol 11 Pages: 1073-1084
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• [Journal Article] Gene and Expression Analyses Reveal Enhanced Expression of Pericentrin 2 (PCNT2) in Bipolar Disorder. (2008)
  • Author(s): Anitha A, Nakamura K, (他20名)
  • Journal Title: Biol Psychiatry 63 Pages: 678-685
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• [Journal Article] Expression of sonic hedgehog regulates morphological changes of rat developing cerebellum in hypothyroidism (2008)
  • Author(s): Hasebe M, Ohta E, Imagawa T, Uehara M.
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• [Journal Article] Changes in cholinergic function in the frontal cortex and hippocampus of rat exposed to ethanol and acetaldehyde (2007)
  • Author(s): Jamal M, Ameno K, Ameno S, Morishita J, Wang W, Kumihashi M, Ikuo U, Miki T, Ijiri I
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• [Journal Article] Takeuchi Y, The effect of prenatal X-irradiation on the developing cerebral cortex of rats. (2007)
  • Author(s): Miki T, Yokoyama T, Sumitani K, Wang ZY, Yang W, Kusaka T, Matsumoto Y, Warita K, Lee NS, Fukui Y
  • Journal Title: A quantitative assessment of glial cells in the somatosensory cortex. Int J Dev Neurosci 25 Pages: 293-297
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• [Journal Article] SNP analyses of growth factor g enes EGF, TGFbeta-1, and HGF reveal haplotypic association of EGF with autism (2007)
  • Author(s): Toyoda T, Nakamura K, (他21名)
  • Journal Title: Biochem Biophys Res Commun 360 Pages: 715-720
  • Peer Reviewed
• [Journal Article] Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism. (2007)
  • Author(s): Nishimura K, Nakamura K, (他20名)
  • Journal Title: Biochem Biophys Res Commun 356 Pages: 200-206
  • Peer Reviewed
• [Journal Article] Qualitative and quantitative studies of the inferior olivary complex in the water buffalo (Buballus bubalis) (2007)
  • Author(s): Rashed R, Emara S, Shinozaki A, Imagawa T, Uehara M.
  • Journal Title: J Vet Med Sci. 69(2) Pages: 143-7
  • Peer Reviewed
• [Journal Article] Oligodendrocyte myelin glycoprotein (OMgp) in rat hippocampus is depleted by chronic ethanol consumption (2006)
  • Author(s): Okamoto H, Miki T, Lee KY, Yokoyama T, Kuma H, Wang ZY, Gu H, Li HP, Matsumoto Y, Irawan S, Bedi KS, Nakamura Y, Takeuchi Y
  • Journal Title: Neurosci Lett. 406 Pages: 76-80
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• [Journal Article] Age-related changes in growth hormone-immunoreactive cells in the anterior pituitary gland of Jcl: Wistar-TgN (ARGHGEN) 1Nts rats (Mini rats) (2006)
  • Author(s): Matsumoto Y, Tsukamoto Y, Miki T, Ogawa K, Lee KY, Yokoyama T, Satriotomo I, Li HP, Gu H, Wang ZY, Karasawa S, Ueda S, Sasaki F, Takeuchi Y.
  • Journal Title: Congenit Anom (Kyoto) 46 Pages: 188-93
  • Peer Reviewed
• [Journal Article] The acute and chronic administration of 8-hydroxy-2-(di-n-propyl amino) tetralin significantly alters the activity of spontaneously active midbrain dopamine neurons in rats (2006)
  • Author(s): Nakamura K, Suzuki K, McCreary AC, Ashby CR Jr.
  • Journal Title: An in vivo electrophysiological study. Synapse 59 Pages: 359-367
  • Peer Reviewed
• [Journal Article] Evidence that variation in the peripheral benzodiazepine receptor (PBR) gene influences susceptibility to panic disorder (2006)
  • Author(s): Nakamura K, Yamada K, (他18名)
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet 141 Pages: 222-226
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• [Journal Article] Interaction between glycogen body cell and neuron: examination in co-culture system (2006)
  • Author(s): Imagawa T, Shogaki K, Uehara M.
  • Journal Title: J Vet Med Sci. 68(10) Pages: 1081-7
  • Peer Reviewed
• [Presentation] Non-vesicular synaptic transport: WGA- HRP and Rab3A-siRNA studies (2010)
  • Author(s): Y akura T, Matsumoto Y, Miki T, Warita K, Wang ZY, Liu JQ, Mamoru F, Takeuchi Y
  • Organizer: 第115回日本解剖学会
  • Place of Presentation: 岩手県民会館
  • Year and Date: 20100328-20100330
• [Presentation] A protein conjugation of WGA essential for transsynaptic tracer in neuronal system: application for Amyloid-βin vivo (2009)
  • Author(s): Takeuchi Y, Matsumoto Y, Miki T, Warita K, Wang ZY, Yakura T, Liu JQ.
  • Organizer: International Symposium on Early Detection and Rehabilitation Technology of Dementia
  • Place of Presentation: 岡山大学
  • Year and Date: 20091211-20091212
• [Presentation] WGA結合タンパクがもたらすシナプス膜輸送機構の新展開 (2009)
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  • Organizer: 第64回日本解剖学会地方会
  • Place of Presentation: 高知大学
  • Year and Date: 20091024-20091025
• [Presentation] WGA-HRPによる順行性シナプス輸送:ラット迷走神経へのRab3A-siRNA投与 (2009)
  • Author(s): 竹内義喜、松本由樹、三木崇範、横山俊史、割田克彦、汪治宇、矢倉富子、藤田守
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 20090916-20090918
• [Presentation] Modulation of hypothalamopituitary axis in Mini rat: further studies with hypophysiotropic somatostatin and gonadotroph (2009)
  • Author(s): M atsumoto Y, Miki T, Tsukamoto Y, Warita K, Wang ZY, Yakura T, Karasawa S, Ueda S, Takeuchi Y.
  • Organizer: The 8th World Congress on Neurohypophysial Hormones
  • Place of Presentation: 北九州国際会議場
  • Year and Date: 20090904-20090908
• [Presentation] Revaluation of anterograde synaptic transport of WGA-HRP in the rat (2009)
  • Author(s): 竹内義喜、三木崇範、横山俊史、松本由樹、割田克彦、汪治宇、上野貴士、藤田守
  • Organizer: 第114回日本解剖学会
  • Place of Presentation: 岡山理科大学
  • Year and Date: 20090328-20090330
• [Presentation] Early postnatal ethanol exposure alters the BDNF and neural interactions in the olfactory bulb. (2008)
  • Author(s): 松本由樹、三木崇範、谷賀、割田克彦、汪治宇、竹内義喜
  • Organizer: 第113回日本解剖学会
  • Place of Presentation: 大分大学
  • Year and Date: 20080327-20070329
• [Presentation] Takeuchi Y Short-term ethanol exposure caused changes in neurotrophins and its receptors expression in mice cerebellum (2007)
  • Author(s): W ang ZY, Miki T, Yokoyama T, Matsumoto Y, Warita K, Sumitani K, Lu F
  • Organizer: 第62回日本解剖学会地方会
  • Place of Presentation: 川崎医科大学
  • Year and Date: 20071027-20071028
• [Presentation] Fos-immunoreactive neurons in the lateral central nucleus of amygdala activated by hypotension with special reference to the parabrachial nucleus in the rat (2007)
  • Author(s): Takeuchi Y, Xie Q, Matsumoto Y, Warita K, Miki T.
  • Organizer: Italian Society of Neuroscience
  • Place of Presentation: Palazzo della Ragione e Palazzo della Gran Guardia
  • Year and Date: 20070927-20070930
• [Presentation] Funa K A nobel enhancer of the PDGF beta-receptor gene activated uring the differentiation of neuroblastoma through GATA factor (2007)
  • Author(s): M atsumoto Y, Kaneko M, Yang W, Watt F, Warita K, Miki T, Takeuchi Y
  • Organizer: Italian Society of Neuroscience
  • Place of Presentation: Palazzo della Ragione e Palazzo della Gran Guardi
  • Year and Date: 20070927-20070930
• [Presentation] Neuroprotective Effects of Rare Sugar against Ethanol Toxicity; An Electron Microscopic Study in Mice Hippocampus. Rare Sugar Congress 2006 in Kagawa (2006)
  • Author(s): Takeuchi Y, Yokoyama T, Miki T, Wang ZY, Yang W, Ueno M.
  • Organizer: The 3rd Symposium of International Society of Rare Sugars, Takamatsu
  • Place of Presentation: かがわ国際会議場
  • Year and Date: 20061121-20061124
• [Presentation] Activity of a novel PDGF b-receptor enhancer during the cel1 cycle and upon differentiation of neuroblastoma (2006)
  • Author(s): Y ang W, Kaneko M, Matsumoto Y, Wang ZY, Yokoyama T, Miki T, Watt F, Funa K, Takeuchi Y.
  • Organizer: 第61回日本解剖学会地方会
  • Place of Presentation: 広島大学
  • Year and Date: 20061111-20061112
• [Presentation] 母子間相互作用の発達神経科学解析;母性剥奪による脳発達への影響 (2006)
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  • Organizer: 第6回日本赤ちゃん学会
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  • Year and Date: 20060329-20060331