| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
We aimed to examine mTOR functions in cerebellar Purkinje cells (PCs) by establishing a mouse model of chronically activated mTOR pathway in PCs. Using constitutively active mTOR, we established double transgenic mice line, in which active mTOR mutant is expressed specifically in PCs (L7-mTOR Tg mice). Immunohistochemical analysis showed that PCs of L7-mTOR Tg mice were remarkably hypertrophied and significantly decreased in their number at 4 weeks of age. Molecularly, L7-mTOR Tg PCs were immunopositive for cleaved caspase 3 and HIF-1alpha, suggesting that PC loss by mTORC1 activation may be caused by apoptotic cell death via hypoxic stress signaling. Behavioral analyses revealed that L7-mTOR Tg mice displayed impaired motor coordination, but normal social behavior. Together, these results indicate that mTORC1 signaling is essential for PC survival and cerebellar functions.
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