| Project/Area Number |
01570603
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Mie University |
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Principal Investigator |
NOMURA Junichi Mie University, School of Medicine, Department of Psychiatry, Professor, 医学部, 教授 (10024720)
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| Co-Investigator(Kenkyū-buntansha) |
MURASE Sumio Mie University, School of Medicine, Department of Physiology, Assistant, 医学部, 助手 (70200285)
OTANI Masato Mie University, Faculty of Education, Assistant Professor, 教育学部, 助教授 (80185298)
KITAYAMA Isao Mie University, University Hospital, Department of Psychiatry, Lecturer, 医学部附属病院, 講師 (70024784)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1990: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Stress / Animal model of depression / Noradrenergic neuron / Locus coeruleus / Electron microscopy / Electrophysiology / In situ viewing / Plasticity / 欝病モデル動物 / ノルアドレナリンニュ-ロン / 青斑核 / 超微形態学 / 電気生理学 / in situ viewing |
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| Research Abstract |
Exposure of female rats to chronic forced walking stress led to an animal model which is analogous to human depression in terms of spontaneous activity, estrus cycle, glucocorticoids secretion and the effect of antidepressants. The function of the ascending noradrenaine (NA) neurons seemed to decrease in the model of depression in view of the decreased tyrosine hydroxylase (TH) activity, the decreased spontaneous firing rate, ultrastructural degenerative changes (destruction of the endoplasmic reticulum membrane etc.) of locus coeruleus (LC), beta-adrenergic receptor down-regulation and the increased NA content in the neurons. Chronic treatment with imipramine restored the spontaneous running activity, but did not the firing rate and the ultrastructural changes. The percentage of LC neurons antidromically activated by cortical stimulation decreased in the model animals. This observation also suggests an axonal degeneration of LC neurons projecting to the cerebral cortex. The fluorescence intensity of catecholamine in the neuron terminals observed by glyoxylic acid method increased in the paraventricular nucleus, the supraoptic nucleus and the hippocampus of the model rats. The structural change of NA neuron fibers in the cerebral cortex stained with dopamine beta-hydroxylase (DBH) antiserum and the percentage of LC neurons retrogradely traced by cortical injection of horseradish peroxydase (HRP) were examined, but their image analysis has not completed yet. In situ viewing of NA neuron terminals and cell bodies by injection of carbocyanine dye (DiI) is now performed. It was been confirmed that DiI injected to the cerebral cortex flows into the LC cells and stays there at least for 3 months.
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