Grant-in-Aid for General Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||SCHOOL OF MEDICINE,KEIO UNIVERSITY|
YOSHIDA Kazunari Sch.of Med.Keio Univ.Instructor, 医学部, 助手 (70166940)
SASAKI Hikaru Sch.of Med.Keio Univ.Assistant, 医学部, 助手 (70245512)
INABA Makoto Sch.of Med.Keio Univ.Assistant, 医学部, 助手 (00245507)
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)
SAGOH Masachika Sch.of Med.Keio Univ.Assistant, 医学部, 助手 (60215704)
各務 宏 慶應義塾大学, 医学部, 助手 (80255471)
大谷 光弘 慶應義塾大学, 医学部, 助手 (80051605)
|Project Period (FY)
1993 – 1995
Completed(Fiscal Year 1995)
|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1993 : ¥700,000 (Direct Cost : ¥700,000)
|Keywords||neurotrophic factor / astrocyte / cytokine / neural regeneration / astrocyte / nerve growth factor / cytokine / neurotrophic factor / cholinergic neuron / interleukin-1 / tumer necresis factor / fibroblaot growth factor / 神経成長因子 / 線維芽細胞成長因子 / インターロイキン-1 / コリン作動性神経細胞 / 副腎皮質ホルモン|
1. Nerve growth kfactor (NGF) and non-NGF-type neurotrophic activities have been found to accumulate transiently in cerebrospinal fluid following surgery. These neurotrophic activites are probably important in the regeneration of damaged neural networks in the central nervous system.
2. A novel neurotrophoc factor which enhances choline acetyltranferase activity of brainstem cholinergic neurons has been shown to exist in astrocyte-conditioned medium. Cytokines such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and acidic fibroblast growth factor (aFGF) increased an amount of the factor released from astrocytes. The factor was revealed to be a heparin-binding protein with a molecular weight of 40-60 kD.
3. Three isoforms (18,22 and 24 kD) of basic fibroblast growth factor (bFGF) are known to be expressed in astrocytes. We have shown that the expression of 22,24-kD isoforms but not of 18-kD isoform in astrocytes is enhanced by cytokines such as IL-1beta, TNF-alph
a and epidermal growth factor (EGF), and that the bFGF content in the cytoplasm of astrocytes is initially ncreased by these cytokines followed by nuclear targeting and localization. In addition, 22-kD isoform has been shown to be released from astrocytes.
4. We have demonstrated that ciliary neurotrophic factor (CNTF) can be released from astrocytes, and that cytokines such as IL-1beta, TNF-alpha and EGF increase CNTF release kfrom astrocytes.
5. Transkforming growth factor-beta1 (TGF-beta1) has been shown to enhance the expression of neural cell adhesion molecule (NCAM) on astrocytes.
These results indicate that as trocytes secrete various neurkotrophicfactors including a novel non-NGF-type neurotrophic factor (s) and so-called non-secretory factors such as bFGF and CNTF,and that the cytokines, which are lilely to be present in the brain following injury, may play an important role in the repair of damaged neunal networks by increasing the expression or release of these neurotrophic factors and cell adhesion molecules by astrocytes Less