| Project/Area Number |
10470202
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Yamanashi Medical University |
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Principal Investigator |
KANBA Shigenobu Yamanashi Medical University, Neuropsychiatry, Professor, 医学部, 教授 (50195187)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Jyunichi Yamanashi Medical University, Neuropsychiatry, Research Associate, 医学部, 助手 (20303422)
KUBOTA Masaharu Yamanashi Medical University, Neuropsychiatry, Research Associate, 医学部, 助手 (60234499)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Interleukine-1 / Tumor Necrosis Factor / vasopressin / Paraventricular Nucleus / ストレス / アンチセンス核酸 / インターロイキン1β / Fyn欠損マウス / cAMP応答配列結合蛋白 / プロテインキナーゼB / Akt / 海馬 |
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| Research Abstract |
Two animal experiments were performed for investigating the effect of cytokines on the pathogenesis of mood disorder.
(1) It is reported that cytokine, one of immune modulating factors, controls the stress response of hypothalamo-pituitary-adrenal axis (HPA axis) in the brain. There are few reports about the effects of cytokines on the vasopressin (VP), which is one of the HPA regulating peptide within the paraventricular nucleus (PVN). In this study, we examined the VP release by the microinjection of cytokines, interleukin-1 (IL-1β), tumor necrosis factor (TNF), interferon (IFN), in the PVN in the rat brain with the microdialysis technique. We also examined the effect of the interleukin-1 receptor antagonist (IL-1Ra) on the cytokine induced VP release. Male Wistar rats (8〜10 weeks old) were anesthetized with urethane (1.4g/kg, ip). Microdialysis probe was implanted into the PVN and samples were collected every 30 minutes. VP was measured by RIA.VP release was stimulated by the IL-1β and TNF, but VP not by IFN.These increases were prevented by the IL-1Ra pre-injection. These results indicate that I1-1β and TNF both regulate HPA axis through IL-1R.
(2) Oligonucleotides targeting M5 muscarinic receptor mRNA were infused for 6 d into the ventral tegmental area of freely behaving rats trained to bar-press for lateral hypothalamic stimulation. M5 antisense oligonucleotide (oligo) infusions increased the frequency required for bar pressing by 48% over baseline levels, with the largest increases occurring after 4-6 d of infusion. Antisense oligo infusions decreased M5 receptors on the ipsilateral, but not the contralateral, side of the ventral tegmentum, as compared with a missense oligo. Therefore, M5 muscarinic receptors associated with mesolimbic dopamine neurons seem to be important in brain-stimulation reward.
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