| Project/Area Number |
16590839
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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 |
Neurology
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| Research Institution | Nagoya City University |
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Principal Investigator |
ITO Jinichi Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (60167260)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Shinji Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (10142192)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Astrocyte / apoE / Cholesterol / FGF-1 / Stress / Probucol / HDL / オートクリン |
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| Research Abstract |
It is known that the astrocytes synthesize and secrete apoE to generate HDL for intercellular cholesterol delivery in the CNS, leading the idea that astrocytes play an important role in cholesterol homeostasis in the CNS. In order to examine pathophysiological relevance of this reaction, we studied association of the production of FGF-1 and apoE in the post-injury mouse brain.
After the spot-injury of the brain by liquid nitrogen, the surface size of the wound shrunk more rapidly in the wild-type mice than the apoE-KO mice. It has been shown that FGF-1 is produced by the astrocytes around the lesion of cryo-injury of the wild mouse brain prior to the increase of apoE synthesis in vivo. Although FGF-1 was produced in the apoE-KO mouse brain, no production of apoE was observed. In the culture system, FGF-1 mRNA increased in rat brain cells in primary culture over three weeks when astrocytes were predominant and neurons mostly disappeared. The astrocytes prepared by one-month primary culture of the rat brain cells followed by one-week secondary culture (M/W cells) expressed FGF-1 mRNA more than the astrocytes prepared by conventional one-week primary and one-week secondary culture (W/W cells). The conditioned media of the M/W cells enhanced release of apoE and cholesterol by the W/W cells, presumably generating HDL. The FGF-1 was identified in the cell lysate of the both types of astrocytes, but the M/W cells released it more into the culture medium. Pretreatment with a goat anti-FGF-1 antibody or heparin depleted the stimulatory activity of the M/W cell conditioned medium. Thus, astocytes are capable of releasing FGF-1 that promotes apoE-HDL production by an autocrine mechanism, showing that FGF-1 is secreted to increase HDL generation from astrocytes by the autcrine mechanism after an exposure to stress or injury.
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