pathophysiological analysis of a mouse model of cerebral leukoencephalopathy and search for pathogenesis-related metabolites
| Project/Area Number |
26860371
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Laboratory medicine
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
yagi mikako 九州大学, ARO次世代医療センター, 学術研究員 (70536135)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | ミトコンドリア / p32/C1qbp / 白質脳症 / p32 / メタボローム解析 / 大脳白質脳症 / C1qbp |
|---|
| Outline of Final Research Achievements |
Mitochondrial dysfunction represents a critical step during the pathogenesis of neurodegenerative disease. The p32/C1qbp gene functions as an essential RNA and protein chaperone in mitochondrial translation, and is indispensable for embryonic development. However, how p32 lead to neurodegeneration remains unclear. Neural-specific p32 deletion resulted in white matter degeneration accompanied by progressive oligodendrocyte loss, axon degeneration and vacuolation in the mid brain and brain stem regions, similar to mitochondrial leukoencephalopathy. Metabolomics analysis showed increased glycolysis, decreased GABA signaling, lipid synthesis and impaired amino acid metabolism in p32cKO tissue. Mitochondrial function in oligodendrocytes and neurons is therefore essential for myelination and axonal maintenance, suggesting that mitochondrial dysfunction contributes to leukoencephalopathy.
|
Report
(4 results)
Research Products
(7 results)
