| Co-Investigator(Kenkyū-buntansha) |
KAMIGUCHI Hiroyuki Sch.of Med., Keio Univ.Assistant, 医学部, 助手 (10233933)
WAKAMOTO Hirooki Sch.of Med., Keio Univ.Assistant, 医学部, 助手 (30230923)
YOSHIDA Kazunari Sch.of Med., Keio Univ.Instructor, 医学部, 助手 (70166940)
KAWASE Takeshi Sch.of Med., Keio Univ.Assistant Professor, 医学部, 講師 (40095592)
OTANI Mitsuhiro Sch.of Med., Keio Univ.Instructor, 医学部, 助手 (80051605)
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| Research Abstract |
This basic research project was conducted to find the way to recovery of the damaged central nervous system. The followings were the results of this project.1) Astrocytes activated by cytokines, including interleukin-1beta, and tumor necrosis factor-alpha, were found to produce a novel neurotrophic factor for brain-stem cholinergic neurons. The neurotrophic factor is a heparin binding protein witch molecular weight is 40-60 kDa. 2) The cytokines promote the release of ciliary neurotrophic factor (CNTF) from astrocytes without enhancing the expression of CNTF in astrocytes. 3) Astrocytes express three major isoforms of basis fibroblast growth factor (bFGF), which molecular weights were 18,22,24kDa, respectively.Cytokines selectively enhance the expression of 22 and 24 kDa isoforms of bFGF.Moreover, the cytokines induce translocation of high molecular bFGF from cytoplasm to nucleus. 4) Transforming growth factor-beta enhances the expression of neural cell adhesion molecule (NCAM) in astrocytes. These results indicate that astrocytes activated by the cytokines promote the regeneration of damaged neural network in the central nervous system. Moreover, we have revealed that adenosine has a neuroprotective effect against ischemic insults in vivo. Propentophylline, which inhibits the uptake of adenosine, the release of dopamine resulting in the restriction of overexcitation in the striatum. Thus, some parts of the mechanism of neuroprotection in the damaged central nervous system was revealed.
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