| Project/Area Number |
17580122
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Food science
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| Research Institution | Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare |
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Principal Investigator |
TANAKA Yasukazu Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Senior research scientist, 東京老人総合研究所, 主任研究員 (40101258)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Machiko Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Research scientist, 東京老人総合研究所, 研究員 (40167284)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Carnitine / Brain / Ischemia / Neuroscience / 神経科学 / 脳虚血 / 神経細胞 / アンチエージング |
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| Research Abstract |
Acetyl-L-carnitine (ALCAR), an acetyl derivatives of L-carnitine and rich in meat, plays a vital roll for energy production from fatty acids in mitochondria in the cells. We have previously demonstrated that aging reduces carnitine contents in the brains(1). Beside it's a role of energy production, carnitine has been indicated to have many physiological effects and used as a curative for many diseases such as cognitive deficits in the patients with AD (2) and senile dementia (3). In this study the neuroprotective effects of ALCAR on ischemic injury and the underling mechanisms were investigated using primary cultured neuronal cells prepared from E18 rat brain cortices and hippocampus slices prepared from aged rats (above 24-month-old). Cultured neuronal cells were exposed to oxygen-glucose deficient condition for 2 hours. After 24 hrs of the ischemic injury, WST-8 test and immuno staining of the cells were carried out to demonstrate ALCAR effects. Pretreatment of the cells with ALCAR significantly increased the survival rates of neuronal cells under ischemic condition with a dose dependent manner. Electrophysiological studies with hippocampus slices showed that ALCAR treatment enhanced recovery of the signals of population spikes and excitatory postsynaptic potential recorded in CAI region of the slices after transient ischemia. ALCAR did not change the levels of brain-derived neurotrophic factor (BDNF) in ALCAR-treated hippocampus slices. Western blot analyses of molecular chaperons, such as HSP70, HO-1, GRP78, Bcl-2, suggested that ALCAR enhances the induction of the proteins. These findings suggest that ALCAR protects the brains from ischemic injury by increasing the induction of stress proteins.
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