| Project/Area Number |
19790236
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
TSUJI Daisuke The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 助教 (00423400)
|
|---|
| Project Period (FY) |
2007 – 2009
|
| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥600,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Keywords | 先天性代謝異常症 / 糖脂質 / グリア細胞 / アストロサイト / ミクログリア / リソソーム病 / 神経変性疾患 / リソソーム |
|---|
| Research Abstract |
Sandhoff disease (SD) is a lysosomal β-hexosaminidase (Hex) deficiency involving excessive accumulation of undegraded substrates, including terminal GlcNAc-oligosaccharides and GM2 ganglioside, and progressive neurodegeneration. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice, and demonstrated the abnormalities of SD-glial cells. We found remarkable differences in the cell proliferation of SD astrocyte (ASD) when compared to cells isolated from wild type mice, with a faster growth rate of ASD cells. In addition, we observed increased ERK phosphorylation in ASD cells, but Akt phosphorylation was decreased. These results indicated that the up-regulation of ERK phosphorylation and the increase in proliferation of ASD astrocytes were dependent upon GM2/GA2 accumulation. Furthermore, inhibitors for PKC and Akt reduced the production of MIP-α or by SD-Micoglia. These findings may represent a mechanism in linking activation of glial cells observed in Sandhoff disease.
|
