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1995 Fiscal Year Final Research Report Summary

Imaging of neurotransmission in humnan brains : Normal and abnormal aging.

Research Project

Project/Area Number 06833002
Research Category

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

Allocation TypeSingle-year Grants
Research Field 老化(加齢)
Research InstitutionTohoku University of Medicine

Principal Investigator

YANAI Kazuhiko  Tohoku University, School of Medicine Pharmacology I,Associate Professor, 医学部, 助教授 (50192787)

Co-Investigator(Kenkyū-buntansha) MEGURO Kenichi  Tohoku University, School of Medicine Assistant Professor, 医学部, 助手 (90239559)
OTSU Hiroshi  Tohoku University, School of Medicine Assistant Professor, 医学部, 助手 (60250742)
Project Period (FY) 1994 – 1995
KeywordsHistamine / Histamine H1 receptor / Aging / Alzheimer disease / PET / human / brain / H3 receptor
Research Abstract

Recently, the histaminergic neuron system in the brain has been clarified and shown to be involved in many physiological functions such as learning. sleep-wakefulness, food intake, drinking, body temperature, neuroendocrine control, and so on. However, there have been few studies on the relationship between the central histaminergic neuron system and aging process. The purpose of our study is to elucidate the role of the central histaminergic neurons in normal and abnormal aging process using multidisciplinary methods from basic and clinical points of view.
(1)The central histaminergic neuron system in rodent models of dementia : The effects of histamine H3 receptor antagonists on learning and memory disability. The histaminergic neuron system in senescence-accelerated mice model (SAM) was examined. The activity of histidine decarboxylase (HDC) was decreased in the cortex of SAM.The level of HDC was restored to that of control after the administration of H3 receptor antagonist to SAM.In addition, learning ability was also improved in SAM after the treatment of H3 antagonists.
(2)Human PET studies of Alzheimer disease. Histamine H1 receptors in humen brains measured using positron emission tomography (PET) : The effects of normal and abnormal aging on H1 receptors were examined using [^<11>C] doxepin as a probe of histamine H1 receptors. Age-related decrease in [^<11>C] doxepin binding was observed by PET.Furthermore, the binding of [^<11>C] doxepin was markedly decreased in cortical tissues of Alzheimer disease when compared with age-and sex-matched controls.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] J. H. Ryu, K. Yanai, et al.: "Ontogenetic development of histamine receptor subtypes in rat brain demonstrated by qunatitative autoradiography." Dev. Brain Res.87. 101-110 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Yanai, J. H. Ryu, et al.: "Histamine H1 receptor occupancy in human brains after single oral doses of histamine H1 antagonists measured by PET" Brit, J. Pharmacol.116. 1649-1655 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Yanai, J. H. Ryu, et al.: "Positron emission tomographic study on central histamine H1 receptor occupancy in human subjects treated with epinastine." Meth. Find. Exp. Clin. Pharmacol.17. 64-69 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J. H. Ryu, K. Yanai, et al.: "Dopamine D1 receptor stimulation reverses the upregulation of histamine H3 receptors following destruction of the ascending dopamine neurons." Brit. J. Pharmacol.(in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Meguro, K. Yanai, et al.: "Effects of thioperamide, a histamine H3 antagonist, on the step-through passive avoidance response in SAM." Pharmacol. Biochem. Behav.50. 321-325 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 谷内一彦,ほか3名: "PETによる脳機能測定:in vivoレセプターマッピング" ブレインサイエンス. 5月号(印刷中). (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Meguro, K.Yanai, N.Sakai, E.Sakurai, K.Maeyama, H.Fukuda, H.Sasaki, and T.Watanabe.: "Effects of thioperamide, a histamine H3 antagonist, on the step-through passive avoidance responce in scenescence accelerated mice (SAM) : Association with increased histidine decarboxylase activity." Pharmacol. Biochem. Behav.50(3). 321-325 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Sakai, K.Yanai, J.H.Ryu, H.Nagasawa, T.Hasegawa, T.Sasaki, K.Kogure, T.Watanabe: "Behavioral studies on rats with transient cerebral ischemia induced by occlusion of the middle cerebral artery." Behavioral Brain Res.(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.H.Ryu, K.Yanai, E.Sakurai, C.-Y.Kim, and T.Watanabe: "Ontogenetic development of histamine receptor subtypes in rat brain demonstrated by quantitative autoradiography" Dev. Brain Res. 87. 101-110 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yanai, J.H.Ryu, T.Watanabe, R.Iwata, T.Ido, Y.Sawai, K.Ito, and M.Itoh: "Histamine H1 receptor occupancy in human brains after single oral doses of histamine H1 antagonists measured by positron emission tomography" Br. J.Pharmacol. 116. 1649-1655 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yanai, J.H.Ryu, T.Watanabe, R.Iwata, T.Ido, M.Asakura, R.Matsumura, and M.Itoh: "Positron emission tomographic study on central histamine H-1 receptor occupancy in human subjects treated with epinastine. a second-generation antihistamine." Meth. Find. Exp. Clin. Pharmacol. 17. 64-69 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.H.Ryu, K.Yanai, X.-L.Zhao, and T.Watanabe: "The effect of dopamine D1 receptor stimulation on the up-regulation of histamine H3 receptors following destruction of the ascending dopaminergic neurons" Brit. J.Pharmacol. (in press). (1996)

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      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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