| Project/Area Number |
09557212
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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 | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
MIYAMOTO Atsushi Sapporo Medical University, Sch. Of Med, Dept. Of Pharmacology, Ass. Prof., 医学部, 助教授 (50166196)
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| Co-Investigator(Kenkyū-buntansha) |
OHSIKA Hideyo Sapporo Medical University, Sch. Of Med, Dept. Of Pharmacology. Prof., 医学部, 教授 (50045358)
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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 |
¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Brain aging / C57BL / 6J mice / Memory disorders / Signal transduction / Membrane fluidity / NMDA receptor / Piracetam / neurosteroids / 老化 / 細胞情報伝達 / マウス / GABA_A受容体 / 受動的回避試験 / 向知性薬 |
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| Research Abstract |
The importance of age-related memory deficits is well known, and much has recently been done to gain a better understanding of the pathophysiology of learning disorders in order to further improve the therapeutical approach. Various ones of evidence suggest that, with aging, there is an impairment of animals' learning abilities.
1) We studied two groups of 30-month-old C57BL/6J mice selected on the basis of their memory performance in the passive avoidance acquisition task (PAAT). By using the PAAT as a test of memory performance, it was found that approximately 50% of aged C57BL/6J mice showed clearly impaired memory performance (AI), whereas about 50% of the aged animals performed clearly unimpaired memory performance (AU) as well as adults (6-month-old). N-methyl-D-aspartate receptor density, as determined by the specific binding of [ィイD13ィエD1H]MK-801 to forebrain membranes, decreased by 27% in AI mice and by 7% in AU mice compared with adult animals. Membrane fluidity, as determined
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by fluorescence probe 1, 6-diphenyl-1,3, 5-hexatriene to forebrain membranes, decreased by 30% in AI mice and by 5% in AU mice compared with adult animals.
2) The antiamnesic and memory-enhancing properties of piracetam and other structurally related nootropics have been demonstrated in numerous studies with animals. Subcutaneous injection of piracetam (200 mg/kg once daily) for 8 weeks improved the impaired memory retention and decreased brain membrane fluidity in AI mice, but had no measurable effect on membrane fluidity in AU mice. It is concluded that chronic administration of piracetam to AI animals promoted a partial recovery of the impaired memory retention with aging, which might be explicable in terms of mechanisms involving fluidity of the brain neuronal membranes.
3) Numerous studies confirm that serum levels of dehydroepiandrosterone sulfate (DHEAS) decrease with age in both human and mammalian and this can be considered to be a rather specific marker of aging. Subcutaneous infection of pregnenolone sulfate (PS) and DHEAS for 8 weeks improved the impaired memory retention of PAAT in AI mice. PS and DHEAS, major neurosteroids that decreases in blood serum with age, may be of use in treatment of neurodegenerative and memory disorders. Less
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