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2000 Fiscal Year Final Research Report Summary

Effects of alcohol and metamphetamine on neurous system : a molecular biological study

Research Project

Project/Area Number 09307018
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionKagawa Medical University

Principal Investigator

SUWAKI Hiroshi  Kagawa Medical University, Faculty of Medicine, Neuropsychiatry, Professor, 医学部, 教授 (10033367)

Co-Investigator(Kenkyū-buntansha) KURODA Shigetoshi  Okayama University, Faculty of Medicine, Neuropsychiatry, Professor, 医学部, 教授 (00093683)
TAKEUCHI Yoshiki  Kagawa Medical University, Faculty of Medicine, Anatomy, Professor, 医学部, 教授 (20116619)
MORIMOTO Kiyoshi  Kagawa Medical University, Faculty of Medicine, Neuropsychiatry, Associate Professor, 医学部, 助教授 (20166432)
FUKUI Yoshihiro  Tokushima University, Faculty of Medicine, Anatomy Professor, 医学部, 教授 (50144168)
TOKUNAGA Akira  Okayama University, Faculty of Medicine, Anatomy, Professor, 医学部, 教授 (40009634)
Project Period (FY) 1997 – 2000
Keywordsalcoholism / acetaldehyde adducts / hippocampus / calmodulin / FAS / antihypnotism / VTA / dopamine
Research Abstract

Acetaldehyde adduct seems to be a risk factor for brain damage in alcohol dependent and withdrawal animals. Furthermore, acetaldehyde adducts production and apoptosis-related gene expression in these animals were elucidated in the present study. On the other hand, abnormal formation of mossy fiber, LTP effects, strong expression of GluR2 subunit, editing of Q/R site and enzyme of CaM dependent phosphatase were observed in the hippocampus. With respect to peptides in the brain, expression of VIP-IR and DNA topoisomerase II β were apparently increased in the cerebral cortex and CA3 pyramidal cells, respectively. Calbindin D28k and GFAP-IR cells were found in the hippocampus and hypothalamus. It was of particularly interest that the expression of IR cells in the SCN of hypothalamus indicated the relationship with circadian rhythm. In FAS animals the ectopic cell mass in the cerebral cortex, abnormal distribution of mossy fibers, developmental anomaly of Purkinje and pyramidal cells and disappear of foot processes of Burgman glia cells were characteristically observed.
In MAP dependent animals the neural plasticity was indicated to have relationship with arc gene, synaptophysin and α-tubulin. Additionally, the pathway of the midbrain VTA-Accumbence nucleus-Prefrontal cortex was also demonstrated to play an important role in abnormal behavior of the animals.

  • Research Products

    (66 results)

All Other

All Publications (66 results)

  • [Publications] Iwahashi K: "Alcohol metabolizing enzymes in Japanese alcoholics."14th IAFS Current Topics in Forensic Science. 1. 32-35 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miki T: "Estimation of the numerical densities of neurons and synapses in cerebral cortex."Brain Research Protocols. 2. 9-16 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tokuda M: "Involvement of calmodulin-dependent protein kinases I and IV in long term potentiation."Brain Res.. 755. 162-166 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩橋和彦: "アルコール依存および離脱症状の脳の病態におけるモデル動物を用いた免疫組織化学的研究-脳内のアセトアルデヒドアダクトー"日本アルコール薬物医学会雑誌. 32. 489-494 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 坂江芳朗: "アルコール依存症におけるCYP2E1の遺伝子型"日本アルコール・薬物医学会雑誌. 32. 541-547 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ameno S: "Dra I site polymorphism of the human CYP2E1(cytochrome P450 2E1) gene and alcoholism."Alcoholism Clinical and Experimental Research. 22. 174A (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwahashi K: "Relationship between alcoholism and CYP2E1 C/D polymorphism."Neuropsychobiology. 38. 218-221 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura K: "Acetaldehyde adducts in the cerebral cortex of etanol-fed mice (withdrawal)."Alcoholism Clinical and Experimental Research. 22. 187A (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe T: "Modification of behavioral responses induced by electrical stimulation of the ventral tegmental area in rats."Behav Brain Res. 93. 119-129 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中村和彦: "アルコール慢性投与における脳内のアセトアルデヒドアダクトについて"日本アルコール・薬物医学会雑誌. 33. 528-529 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中村和彦: "非活性型アルデヒド脱水素酵素ALDH2^*2を有するアルコール依存症の特徴-個々の臨床特徴とアルコール代謝酵素について-"精神医学. 40(5). 531-537 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 洲脇寛: "アルコール依存症とcytochrome P450 2E1(CYP2E1)の遺伝子多型性に関する研究"厚生省精神・神経疾患研究委託費アルコール依存の分子生物学的研究,平成9年度研究報. 37-39 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉原英児: "ALDH2(ALDH2^*1/2)およびCYP2E1(c1/c2,C/D)の遺伝子多型がアルコール代謝速度に及ぼす影響"臨床遺伝研究. 20. 109-114 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Irawan S: "Effect of short-term ethanol exposure on the suprachiasmatic nucleus of hypothalamus : immunohistochemical study in mice."Brain Research. 847. 124-129 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miki T: "The effect of the timing of ethanol exposure during early postnatal life on total number of Purkinje cells in rat cerebellum."J.Anat.. 194. 423-431 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miki T: "Abnormal distribution of hippocampal mossy fibers in rats exposed to X-irradiation in utero."Developmental Brain Research. 112. 275-280 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 森本清: "精神分裂病周辺群の脆弱性-妄想性障害のドパミン機構と分子遺伝学-"脳と精神の医学. 10(2). 139-152 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中野太郎: "アルコール慢性投与マウスの脳内のアセトアルデヒドアダクトについて"日本アルコール・薬物医学会雑誌. 34(6). 549-557 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 洲脇寛: "アルコール関連脳障害の分子遺伝学的研究"平成10年度厚生省神経・精神疾患研究委託費による研究報告書. 160-161 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉原英児: "アルコール依存症におけるセロトニンレセプターの遺伝子型(HTR2 MspI polymorphism)"日本アルコール・薬物医学会雑誌. 34. 459-464 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Irawan S: "Short-term ethanol exposure alters calbindin D28k and glial fibrillary acidic protein immunoreactivity in hippocampus of mice."Brain Research. 879. 55-64 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwahashi K: "The human serotonin receptor gene (HTR2) MspI polymorphism in Japanese schizophrenic and alcoholic patient."Neuropsychobiology. 41. 124-126 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Komatsu S: "Ectopic cell mass in the cerebral cortex following prenatal exposure to alcohol (abs)."Teratology. 62(3). 42A, (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miki T: "Neurons in the hilus region of the rat hippocampus are depleted in number by exposure to alcohol during early postnatal life."Hippocampus. 10. 284-295 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miki T: "A stereological analysis of the effect of early postnatal ethanol exposure on neuronal numbers in rat dentate gyrus."Image Analysis and Stereology. 19. 99-104 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura K: "Immunohistochemical study on acetaldehyde adducts in alcohol-fed mice."Alcoholism : Clinical and Experimental Research. 24. 93-96 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura K: "Characteristics of Japanese alcoholics with inactive aldehyde dehydrogenase 2^*2 : clinical features of alcoholics with ALDH2^*2."Addiction Biology. 5. 307-311 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato K: "Increased synapsin I protein immunoreactivity during long-term potentiation in the rat hippocampus."Brain Res. 872. 219-222 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshihara E: "The effect of the ALDH2^*1/2, CYP2E1 C1/C2 and C/D genotypes on blood ethanol elimination"Drug and Chemical Toxicology. 23. 371-379 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Komatsu S: "Prenatal exposure to ethanol induces leptomeningeal heterotopia in the cerebral cortex of the rat fetus."Acta Neuropathologica. 101(1). 22-26 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 筒井公子: "細胞工学"秀潤社. 8 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 森本清: "精神科ケースライブラリー"中山書店. 13 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中村和彦: "アルコールと医学生物学"東洋書店. 6 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwahashi K: "Alcohol metabolizing enzymes in Japanese alcoholics"14th IAFS Current Topics in Forensic Science. 1. 32-35 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miki T: "Estimation of the numerical densities of neurons and synapses in cerebral cortex."Brain Research Protocols. 2. 9-16 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokuda M: "Involvement of calmodulin-dependent protein kinases I and IV in long term potentiation."Brain Res.. 755. 162-166 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwahashi K: "Acetaldehyde adducts in the cerebral cortex of ethanol-fed mice (immunohistochemical staining for acetaldehyde adducts using the antibody against acetaldehyde adducts)."Nihon-Arukoru-Yakubutsu-Igakkai-Zasshi. 32. 498-494 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakae Y: "Relationship between alcoholism and CYP2E1 genotypes."Nihon -Arukoru-Yakubutsu-Igakkai-Zasshi. 32. 541-547 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ameno S: "Dra I site polymorphism of the human CYP2E1 (cytochrome P450 2E1) gene and alcoholism."Alcoholism Clinical and Experimental Research. 22. 174A (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwahashi K: "Relationship between alcoholism and CYP2E1 C/D polymorphism."Neuropsychobiology. 38. 218-221 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura K: "Acetaldehyde adducts in the cerebral cortex of etanol-fed mice (withdrawal)."Alcoholism Clinical and Experimental Research. 22. 187A (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe T: "Modification of behavioral responses induced by electrical stimulation of the ventral tegmental area in rats."Behav Brain Res. 93. 119-129 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura K: "Acetaldehyde adducts in the cerebral cortex of chronic ethanol-fed mice."Nihon-Arukoru-Yakubutsu-Igakkai-Zasshi. 33. 528-529 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura K: "Characteristics of Japanese alcoholics with the atypical aldehyde dehydrogenase 2^*2"Clinical Psychiatry. 40(5). 531-537 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suwaki H: "Relationship between alcoholism and cytochrome P-450 2E1(CYP2E1) polymorphism."The report of neuropsychiatric study : molecular biology of alcoholism (H10 Department of health and human services fundation). 37-39 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yhoshiwara E: "The effects of the ALDH2^*1/2, CYP2E1 C1/C2 and C/D genotypes on blood ethanol elimination."Rinsho iden kenkyu. 20. 109-114 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Irawan S: "Effect of short-term ethanol exposure on the suprachiasmatic nucleus of hypothalamus : immunohystochemical study in mice."Brain Research. 847. 124-129 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miki T: "The effect of the timing of ethanol exposure during early postnatal life on total number of Purkinje cells in rat cerebellum."J.Anat.. 194. 423-431 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miki T: "Abnormal distribution of hippocampal mossy fibers in rats exposed to X-irradiation in utero."Developmental Brain Research. 112. 275-280 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morimoto K: "Vulnaerability of schizophrenia spectrum disorder (dopaminergic mechanisms and molecular genetics of delusional disorder)."Brain Science and Mental Disorders. 10(2). 139-152 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano T: "Acetaldehyde adducts in the cerebral cortex of long-term etanol-fed model."Nihon-Arukoru-Yakubutsu-Igakkai-Zasshi. 34(6). 549-557 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suwaki H: "Molecular genetics of alcohol related encephalopathy."The report of neuropsychiatric study (H10 Department of health and human services fundation). 160-161 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshiwara E: "Relationship between alcoholism and HTR2 MspI polymorphism."Nihon-Arukoru-Yakubutsu-Igakkai-Zasshi. 34. 459-464 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Irawan S: "Short-term ethanol exposure alters calbindin D28k and glial fibrillary acidic protein immunoreactivity in hippocampus of mice."Brain Research. 879. 55-64 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwahashi K: "The human serotonin receptor gene (HTR2) MspI polymorphism in Japanese schizophrenic and alcoholic patient."Neuropsychobiology. 41. 124-126 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Komatsu S: "Ectopic cell mass in the cerebral cortex following prenatal exposure to alcohol (abs)."Teratology. 62(3). 42A (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miki T: "Neurons in the hilus region of the rat hippocampus are depleted in number by exposure to alcohol during early postnatal life."Hippocampus. 10. 284-295 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miki T: "A stereological analysis of the effect of early postnatal ethanol exposure on neuronal numbers in rat dentate gyrus."Image Analysis and Stereology. 19. 99-104 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura K: "Immunohistochemical study on acetaldehyde adducts in alcohol-fed mice."Alcoholism : Clinical and Experimental Research. 24. 93-96 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura K: "Characteristics of Japanese alcoholics with inactive aldehyde dehydrogenase 2^*2 : clinical features of alcoholics with ALDH2^*2."Addiction Biology. 5. 307-311 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato K: "Increased synapsin I protein immunoreactivity during long-term potentiation in the rat hippocampus."Brain Res. 872. 219-222 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshihara E: "The effect of the ALDH2^*1/2, CYP2E1 C1/C2 and C/D genotypes on blood ethanol elimination"Drug and Chemical Toxicology. 23. 371-379 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Komatsu S: "Prenatal exposure to ethanol induces leptomeningeal heterotopia in the cerebral cortex of the rat fetus."Acta Neuropathologica. 101(1). 22-26 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsutsui K: "Roles of Topoisomerase II β in Brain Development."Cell Technology 16(11), Shuiunsha Co., Ltd.. 1625-1632 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morimoto K: "Alcohol substance abuse and intoxycation (H.Suwaki edit)"Psychiatric case library IV, Nakayama Publisher. 195-207 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura K: "Alcohol related disorder and acetaldehyde adducts."Alcohol and medical biology (Alcohol medical biological society), Toyo Publisher. 90-95 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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