| Project/Area Number |
09357019
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NOMURA Yasuyuki Hokkaido Univ., Grad. School of Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (00034041)
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| Co-Investigator(Kenkyū-buntansha) |
SHUTO Satoshi Grad. School of Pharm. Sci., Hokkaido University, Associate Prof., 大学院・薬学研究科, 助教授 (70241346)
MURAYAMA Toshihiko Grad. School of Pharm. Sci., Hokkaido University, Associate Prof., 大学院・薬学研究科, 助教授 (90174317)
OKUMA Yasunobu Grad. School of Pharm. Sci., Hokkaido University, Associate Prof., 大学院・薬学研究科, 助教授 (20127939)
HATTORI Masao Research Institute for Oriental Med., Toyama Medical & Pharmaceutical Univ., Prof., 和漢薬研究所, 教授 (40126545)
UEHARA Takashi Grad. School of Pharm. Sci., Hokkaido University, Associate Prof., 大学院・薬学研究科, 助手 (00261321)
松田 彰 北海道大学, 大学院薬学研究科, 教授 (90157313)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥35,300,000 (Direct Cost: ¥35,300,000)
Fiscal Year 1999: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1998: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 1997: ¥19,000,000 (Direct Cost: ¥19,000,000)
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| Keywords | senescence accelerated mouse / learning impairments / depressive behavior / ischemia / neuronal death / GDNF / aging / 加齢 / senescence accelerated mouse(SAM) / differential display法 / グルタミンシンテターゼ / 促進老化マウス / 虚血モデル / 神経伝達物質 / 受容体 / ストレス刺激 / アポートシス / NO |
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| Research Abstract |
The senescence accelerated mouse (SAM) is known as a murine model of aging. SAM consists of senescence accelerated-prone mouse (SAMP) and senescence accelerated-resistant mouse (SAMR). Previously, we reported that SAMP8 and SAMP10 exhibit age-related learning impairments . In this study, we investigated the changes in emotional behavior and in neurotansmitter receptor in SAMP10, and the effect of onion extract on learning ability in Morris's water maze test.
1) SAMP10 at 8 months showed an increases of immobility in a forced swimming test compared with SAMR1. Treatment with desipramine (25 mg/kg, I.p., 3 days) in SAMP10 caused a decrease in immobility.
2) In the cortex from SAMP1O, [ィイD13ィエD1H]quinpirol binding to D2/D3 dopamine receptors increased significantly. In the hippocampus from SAMP10, [ィイD13ィエD1H]hydroxy DPAT binding to 5-HTィイD11AィエD1 receptors increased.
3) In Morris's water maze task, in a control strain of SAMR1 at 8 months, the escape latency and path length decreased with increasing trial days, in contrast, the escape latency and path length did not change in SAMP8. Treatment with onion extract (5 ml/kg, p.o., 2 months) in SAMP8 improved the learning and memory in the task.
4) In the control rats pretreated with the vehicle, transient forebrain ischemia-induced delayed neuronal death in the hippocampal CA 1 region was observed 7 days after reperfusion. Pretreatment with glial cell line-derived neurotrophic factor (1 μg), which was directly microinjected into the right hippocampal CA1 region, gave significant protection against the neuronal death. CV-159 (a dihydropyridine derivative) that blocks the L-type CaィイD12+ィエD1 channel and inhibits the calmodulin-dependent pathway. CV-159 gave protection against delayed neuronal death in the CA1 region after 15-min transient forebrain ischemia.
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