| Project/Area Number |
18500286
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
SAKURAI Eiko Tohoku University, Tohoku, University, Graduate School of Medicine, Assistant Professor (90153949)
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| Co-Investigator(Kenkyū-buntansha) |
YANAI Kazuhiko Tohoku, University, Graduate School of Medicine, Professor (50192787)
WATANABE Takehiko Tohoku, University, Honor Professor (70028356)
YAMAZAKI Hiromichi Tohoku, University, Cyclotron and Radioisotope Center, Professor (00166654)
OKAMURA Nobuyuki Tohoku, University, Graduate School of Medicine, Assistant Professor (40361076)
KURAMASU Atsuo Tohoku, University, Graduate School of Medicine, Lecture (90302091)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,140,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | histaminergic neuron system / mice / stress / childhood / learning / memory / atypical anti-psychotics / neurogeneses / in-air micro PIXE / 大気マイクロPUXE |
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| Research Abstract |
It is known that childhood stress carries a significant risk for a variety of problems involving cognition and behavior. Early social isolation rearing from the age of wearing (21-28 days) into adulthood has been often used as an appropriate environmental factor to produce animal models with negative symptoms of schizophrenia. Previous studies have shown that both the cholinergic and histaminergic neuron systems are in many physiological functions including learning and memory. However, it is still unclear how and what existent central histaminergic transmission is involved in the phathophysiology of psychiatric diseases. In this study, we examined 6 topics as follows; 1. Whether the blockade of multiple histamine receptors has any significant effects on the survival of life and health? 2. Animal model of the early social isolation and the behavioral change in the mice. 3. The effects of antipsychotic drugs on the mice subjected social isolation. 4. An imaging of neurogenesis in mice brain by in air micro-PIXE method. 5. The measurement of the bromine ions in the brain slices in the social isolation mice. 6. Effects of isolation stress on monoamines and their metabolite contents in the brain. From these experiments, blockade of H1 receptor-mediated neurotransmission attenuates social isolation-induced behavioral changes and the therapeutic effects of atypical anti-psychotics are mediated, at least in part, by interaction with H1 receptors in the brain. BrdU labeling hippocampal neurogeneses were observed in the brain slices of H1KO and WT mice by use of in-air micro PIXE analysis. The amount of bromine in the case of H1KO mice is small compared with WT mice. H1, H2, H3 triple histamine receptors gene deficient mice and HI, H3 double histamine receptors knockout mice were born and alive. However, H2 receptor-related multiple histamine receptors genes knockout mice were difficult to make, although the reasons were unknown.
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