| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
We generated mice with a cathepsin D (CTSD) deficiency specifically in the Purkinje (PCs) and basket cells (BCs) and compared their phenotypes with those of PC and BC-selective Atg7-deficient mice. In both strains of mice, PCs underwent degeneration, but the CTSD-deficient PCs disappeared more rapidly than their Atg7-deficient counterparts. The neuronal cell death of CTSD- and Atg7-deficient PCs was distinct from apoptosis. Axonal spheroids and the swelling of presynaptic terminals of PCs were more pronounced in Atg7-deficient PCs than in CTSD-deficient PCs.These results suggested that PCs were more vulnerable to CTSD deficiency in lysosomes than to autophagy impairment, and this vulnerability does not depend on the severity of axonal swelling.
We also generated mice with a Golgi pH regulator (GPHR) deficiency specifically in the PCs and BCs and found that PCs from the mutant mice exhibited axonal degeneration and progressive cell loss.
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