| Project/Area Number |
13470512
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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 |
応用薬理学・医療系薬学
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
WATANABE Hiroshi Inst. of Natural Medicine Dept. of Pharmacology Professor, 和漢薬研究所, 教授 (10012642)
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| Co-Investigator(Kenkyū-buntansha) |
TOHDA Michihisa Inst. of Natural Medicine Dept. of Pharmacology Instructor, 和漢薬研究所, 助手 (20207525)
MATSUMOTO Kinzo Inst. of Natural Medicine Dept. of Pharmacology Associate Professor, 和漢薬研究所, 助教授 (10114654)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | learning and memory / bilateral common carotide arteries / differential display / cloning / oxindole alkaloids / pH-sensitive liposome / antisense / Xenopus oocyte / 痴呆 / 遺伝子発現 / RT / PCR / 釣藤散 / ツメガエル卵母細胞 / セロトニン / 興奮性アミノ酸 / 遺伝子発現変化 / 水迷路 / 青班核 / ノルァドレナリン神経系 |
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| Research Abstract |
The rat with chronic cerebral hypoperfusion which is produced by permanent occlusion of bilateral common carotide arteries (2VO) is a useful model to study for dementia. The 2VO rat exhibited impairment of learning and memory behavior and histological rarefaction in the white matter of the brain. To isolate the intrinsic factors in the brain which induce dementia and rarefaction, the differential display method (DD) was applied to mRNAs isolated from 2VO- and sham-operated rat brains for 4 days. One of the factors which dramatically changed the expression was detected and it named vof-21. Although the clarified sequence by DD was only 415 nt, the whole sequence of vof-21, 4,885 nt, was also recloned. Vof-21 sequence was a novel and the sequence was submitted to gene bank, No. AB089205. The expression was shown a peak at 7 days after 2VO, and then decreased to the sham level at 35 days. The expression was abundant in the brain and the lung followed by in the thymus. The results of in si
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tu hybridization revealed that the expressions in brain were rich in locus coreuleus, pontine nucleus and hippocampus. The RT/PCR shows that vof-21 mRNA also existed in NG108-15 cells. To inhibit the expression in this cells, the conditions of pH-sensitive liposome methods were established and reported. The functional significance of vof-21 was still studying by using of this liposome system especially on Ca2+ and other ion channel and/or mobility. Several studies demonstrated that some of the oxindole alkaloids of Uncaria species have the memory improving and neuroprotective effect in the animal models. Therefore, the effects of Uncaria alkaloids on the neurotransmitter receptor functions were studied by using the electrophysiolgical system to clarify the possible mechanisms underlying the neuropharmacological actions. The results show that pentacyclic oxindole alkaloids (pteropodine and isopteropodine)enhanced the electrophysiological response induced by M1 and 5-HT2 receptor activation in Xenopus oocyte injected brain RNA. On the other hand, tetracyclic oxindole alkaloids (rhynchophylline and isorhynchophylline) inhibited NMDA response. It has been well known that muscarinic receptor inhibition and NMDA receptor stimulation induced dementia and neuronal cell death, respectively. Thus these mechanisms of oxindole alkaloids have some roles for anti-dementia effects. Less
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