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Neurochemical and Pharmacological Studies on the Disturbances in Serotonergic systems in Alzheimer-type Dementia

Research Project

Project/Area Number 03454293
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionJuntendo University School of Medicine

Principal Investigator

ARAI Heii  Juntendo University School of Medicine, Lecturer, 医学部, 講師 (50167988)

Co-Investigator(Kenkyū-buntansha) KIMURA Michihiro  Juntendo University School of Medicine, Asistant, 医学部, 助手 (50234381)
NOGUCHI Iwahide  Juntendo University School of Medicine, Asistant, 医学部, 助手 (30237820)
MINAMI Masayuki  Juntendo University School of Medicine, Asistant, 医学部, 助手 (50229770)
IWAMOTO Norihiko  Juntendo University School of Medicine, Asistant, 医学部, 助手 (60211067)
ICHIMIYA Yosuke  Juntendo University School of Medicine, Lecturer, 医学部, 講師 (10184631)
河村 哲  順天堂大学, 医学部, 助手 (20204779)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1991: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsAlzheimer's disease / Senile Dementia / Neurotransmitter / Serotonin / Neuropeptide / Human Brain / アルツハイマ-病
Research Abstract

Neurochemical and pharmacological investigations were performed on rat brains and postmortem human brains obtained from Alzheimer-type dementia(ATD) patients in order to understand the pathogenesis of ATD.Selective serotonin reuptake inhibitor(ZD211) given orally(30mg/kg) decreased corticotropin releasing factor-like immunoreactivity(LI) and increased galanin-LI in rat hypothalamus, adorenocorticotropic hormone-LI in serum and corticosteron-LI in serum. These findings suggest the stimulation of hypothalamus-pituitary-adrenal cortex axis by the serotonergic system. Neurochemical examinations on postmortem brains revealed that changes in the cholinergic and serotonergic systems in the early-onset ATD brains were much severer than those in the late-onset ATD brains. These findings as well as changes in neuropeptides in ATD brains may suggest the usefulness of serotonin reuptake inhibitors as a therapeutic drug for ATD patients, in particular the early-onset ATD subgroup. We also examined the correlations between biogenic amine concentration in brain and those in plasma. However, none of the peripheral marker except for homovanillic acid was found to be useful to understand changes in brains. Another clinical finding found in the present study was the wide variations of plasma-concentrations of brain metabolism-activating agents in patients with organic brains disorders. These features should be taken into considerations when serotonergic drugs are induced clinically for ATD patients. In conclusion, it was suggested that the serotonergic system as well as the interactions between neurotransmitters should receive attention in terms of therapeutic strategies for ATD.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Minami M.: "A disorganized increase of galanin-like immunoreactivity in cerebral cortex of Alzheimer-type dementia brains" J.Neural Transm[P-D Sect]. 4. 285-292 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Noguchi I.: "A study on postmortem stability of vasopressin mRNA in rat brain compared with those in total RNA and ribosomal RNA" J.Neural Transm[Gen.Sect]. 83. 171-178 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Neurotransmitter changes in early-and late-onset Alzheimer-type dementia" Prog Neuropsychopharmacol Biol Psychiat. 16. 883-890 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 新井平伊: "アルツハイマー病脳の神経伝達物質異常" 代謝. 29. 287-292 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 新井平伊: "アルツハイマー病とアルツハイマー型老年痴呆は同一疾患か" Annual Review神経'94. 211-216 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minami M.: "A preliminary study of plasma concentrations of bifemelane,indeloxazine and propentofylline in aged patients with organic brain disorders" Prog Neuropsychopharmacol Biol Psychiat. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Frontiers in Alzheimer Research" Elsevier, 301 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "β-amyloid precursor proteins and neurotransmitter function" Excerpta Medica, 243 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minami M.: "A disorganized increase of galanin-like immuno-reactivity in cerebral cortex of Alzheimer-type dementia brains." J.Neural Transm[P-D Sect]. 4. 285-292 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Noguchi I.: "A study on postmortem stability of vasopressin mRNA in rat brain compared with those in total RNA and ribosomal RNA" J.Neural Transm. 83. 171-178 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Neurotransmitter changes in early- and late- onset Alzheimer-type dementia" Prog.Neuropsychopharmacol Biol Psychiat. 16. 883-890 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Neurotransmitter abnormalities in Alzheimer-" Taisya. 29. 287-292 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Iwamoto N.: "Long-term memory and calpain" Dementia. 7. 16-19 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Neuropeptide abnormalities in Alzheimer-type dementia brains" Frontiers in Alzheimer Research, Elsevier. 301 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Changes in galanin in Alzheimer-type dementia brains." Beta-amyloid precursor proteins and neurotransmitter function, Excerpta Medica. 243 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Postmortem human brain tissue investigation of Neurotransmitters in aging and AD/SDAT" Biological Psychiatry Elsevier. 949 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Presenile and senile dementia" Today's Diagnosis Igaku Syoin. 1832 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arai H.: "Alzheimer's disease and Senile dementia of Alzheimer-type" Annual Review ヤSinkei' Tyugai Igaku. 250 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Noguchi I.: "A study on postmortem changes in vasopressin mRNA in rat brain using a non-isotopic method" Basic, Clinical and The-peutic Aspects of Alzheimer's and Parkinson's Disease Plenum Press. 290 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 新井,平伊: "アルツハイマー病とアルツハイマー型老年痴呆は同一疾患か" Annual Review神経'94. 211-216 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Minami M.: "A preliminary study of Plasma concentratlous of Bifemelane,Indeloxazine,and Propentofylline in Aged Patients with Organic Brain Disorders" Prog.Neuropsychopharmacol Biol Psychiat. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] 新井,平伊: "医学書院(分担執筆)" 今日の診断指針. 1832 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Arai H: "Neurotransmitter changes in early-and late-onset Alzheimer-type dementia" Prog Neuropsycho Blol Psych. 16. 883-890 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 新井 平伊: "アルツハイマー病脳の神経伝達物質異常" 代謝. 29. 287-292 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Arai H: "Effects of citalopram,5-HT reuptake inhibitor,on hypothalamic-pituitary-adrenal(HPA) axis in rats" Clin Neuropharmacol. Supl.1. 581- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Minami M: "Plasma concentration of anti-dementia drugs in aged patients" Clin Neuropharmacol. Supl.1. 507- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 岩本 典彦: "長期記憶とカルペイン" Dementia. 7. 16-19 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Arai H: "Parvalbuminーimmunoreactive neurons in the cortex in Pink's diseace" J.Neurol. 238. 200-202 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Minami M: "A disorganized increase of galaninーlike immunoreactivity in cerebral cortex of Alzheimerーtype dementia brains" J.Neural Transm[PーD Sect.]. 4. 285-292 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Noguchi I: "A study on postmortem stability of vasopressin mRNA in rat brain compared with those in total RNA and ribosomal RNA" J.Neural Transm. 83. 171-178 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Arai H: "Neuropeptide abnormalities in Alzheimerーtype dementia brains.In Frontiers in Alzheimer Research" Elsevier(Eds.T.Ishii et al.), 301 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Arai H: "Changes in galanin in Alzheimerーtype dementia brains.In βーamyloid precursor proteins and neurotransmitter function" Excerpta Medica(Ed.M.Kameyama), 97 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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