| Project/Area Number |
07458211
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
|---|
Principal Investigator |
OOHIRA Atsuhiko Department of Perinatology, Head, 周生期学部, 部長 (20101074)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MATSUI Fumiko Department of Perinatology, Assistant, 周生期学部, 助手
WATANABE Eiji Department of Perinatology, Researcher, 周生期学部, 研究員 (30250252)
|
|---|
| Project Period (FY) |
1995 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥3,200,000 (Direct Cost: ¥3,200,000)
|
|---|
| Keywords | proteoglycan / neurogycan C / N-syndecan / heparan sulfate / brain / neurite outgrowth / growth factor / bFGF / プレイオトロフィン / ニューロカン / 神経回路 / 神経再生 / 脳損傷 / 小脳 / 嗅神経線維 / モノクローナル抗体 / シナプス |
|---|
| Research Abstract |
To examine the involvement of cell surface heparan sulfate proteoglycans (HSPGs) in the growth factor signaling in the brain development, identification of HSPGs were perrormed with monoclonal antibodies (MAbs) against membrane-bound proteoglycans prepared from 10-day-old rat brains. Four MAbs recognized a 150 kDa chondroitin sulfate proteoglycan with a 120 kDa core glycoprotein. Molecular cloning of the core protein revealed that the proteoglycan, designated neuroglycan C (NGC), is a novel transmembrane proteoglycan. Other three MAbs recognized N-syndecan, a transmembrane heparan sulfate proteoglycan with a 140 kDa core glycoprotein.
The expression of N-syndecan was spatially and temporally regulated in the central nervous system. Westem blot analysis revealed that the peak level of expression was oserved in the rat brain during the period from postnatal days 0 to 20 when neuritogenesis and synaptogenesis occur most extensively. Immunohistochemical studies showed that N-syndecan was associated mainly with the actively growing nerve fibers in the developing brain. In the adult rat, high-level expression was exceptionally recognized on the olfactory nerves and glomeruli, when the renewal of both axons and synapses is occurring constantly.
N-syndecan spotted on a PVDF membrane bound some heparin-binding growth factors such as basic fibroblast growth factors (bFGF), pleiotrophin (HB-GAM) and hepatocyte growth factor (HGF), which can promote neurite outgrowth from primary-cultured neurons. Digestion of N-syndecan with heparitinase I resulted in the failure of the binding to these growth factors. These findings, together with the results of immunohistochemistry, suggest that N-syndecan would catch the heparin-binding growth factors with the neurite-promoting activity of the growing nerve fibers, and that it would be involved in the signal transduction of these growth factors to stimulate the axonal growth.
|
