The machanism of oligodendroglial apoptosis of in the model of the genetic demyelination.
| Project/Area Number |
11670761
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
TANIIKE Masako Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30263289)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MOHRI Ikuko Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
SHIMA Masaaki Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (10252660)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Twitcher / domyolination / oligedendroglia / Apoptosis / necrosis / TNF-α / Cerebellum / microglia / カスパーゼ / pi-GST |
|---|
| Research Abstract |
The twitcher mouse is an authentic model of a human Krabbe disease, which is caused by the deficiency of galactosylceramidase. After postnatal day 30, the number of oligodendroglia progressive decreased with resultant demyelination in the CNS.
In this study, we first found out that oligodendroglia in the twitcher cerebrum were depleted by apoptosis judgeby the morphological criteria as well as the presence of TUNEL-positive oligodendroglia and DNA laddering. However, oligodendroglia in the spinal cord was suggested to take a necrotic pathway rather than apoptosis leading to the cell death. Thus, even if thebasic defect is common to all twitcher oligodendroglia, the environmental factors may decide what pathways they take to the eventual death.
We also recognized that TNF-α, a well-established apoptotic molecule in vitro, became expressed in concordance with the progression of demyelination in the twitcher brains, whereas TNF-α is not expressed in the age-matched normal controls. Double labeling revealed that TNF-α was expressed in activated microglia/macrophages in the twitcher brains, especially in the cerebellar white matter and the cerebellopontine angle. These sites were severely demyelinated with a lot of apoptotic oligodendrocytes. These lines of evidence indicated that the apoptosis of oligodendroglia in these lesions was progressed via the TNF-α-mediated pathway. We are now investigating the downstream cascade following the TNF-α induction in activated microglia.
To know the exact mechanism how oligodendroglia die may make the rational therapy available for this genetic demyelination.
|
Report
(3 results)
Research Products
(12 results)
