| Project/Area Number |
06454151
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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 |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Toyama University |
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Principal Investigator |
SASAKI Kazuo Toyama Univ., Fac.of Engineering, Professor., 工学部, 教授 (60042826)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKUDA Akira Toyama Univ., Fac.of Engineering, Assistant., 工学部, 助手 (40236849)
KAWARADA Atsushi Toyama Univ., Fac.of Engineering, Associate Professor., 工学部, 助教授 (80195164)
OOMURA Yutaka Nippon Zoki Pharmaceu.Co., Inst.of Bio-Active Science, Advisor., 生物活性研究所, 顧問 (30019517)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | Fibroblast Growth Factor / Food Intake / Paraventricular Nucleus / Learning / Memory / CRF / Medial Septum / Senescence / 内側手綱核 / 老化促進モデルマウス / 長期増強 / 黒質ドーパミンニューロン / 副腎 / 視索上核 |
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| Research Abstract |
(1) Intracerebroventricular (i.c.v.) infusion of some N-terminal fragments of acidic fibroblast growth factor (aFGF) such as aFGF (1-20) and aFGF (1-29) had no effect on food intake in rtas. However, infusion of [Ala^<16>] aFGF (1-29), in which a cysteine residue at position 16 was replaced by an alanine residue, significantly decreased food intake. In contrast, intrahypothalamic infusion of anti-FGF receptor-1 antibody increased food intake.
(2) Intraperitoneal (i.p.) injection of glucose, which increases aFGF level in the cerebrospinal fluid, facilitates learning and memory in mice when tested by passive avoidance and Morris water maze tasks. This glucose effect was abolished by i.c.v.anti-aFGF antibody infusion 30 min before the i.p.glucose injection.
(3) Effect of aFGF and aFGF(1-15) on neuronal activity in the parvocellular part of the paraventricular nucleus (PPPVN) in the hypothalamus was investigated in rat slice experiment. Both peptides increased the activity in more than half of PPPVN neurons. The result suggest that aFGF and aFGF (1-15) activate the hypothalamo-pituitary-adrenal axis, since PPPVN includes many CRF-containing neurons.
(4) In senescence accelerated mouse (SAMP/8) which is known in deteriorating ability of learning and memory with age, subcutaneous injection of aFGF and [Ala^<16>] aFGF (1-29) was continued for 9 months at a frequency of once a week. In control SAMP/8, cell death and decrease of ChAT activity were observed in medial septum cholinergic neurons. These deficits were blocked in peptide-treated SAMP/8 and impairment of learning and memory seen in control SAMP/8 was ameliorated.
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