| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Recently, we have found that microsomal PGE synthase (mPGES)-1 plays a crucial role in dopaminergic neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of parkinson’s disease (PD). mPGES-1 was expressed in dopaminergic neurons, but not in microglia and astrocytes, in substantia nigra (SN). We found that mPGES-1 contributes not only to dopaminergic neuronal death through production of PGE2, but also to reduction in dopamine content, impairment of nitro-striatal projection and behavioral disorder assessed by Rotarod test. Furthermore, using in vitro and in vivo PD models, we found that EP3 receptors may have crucial role in mPGES-1 neurotoxicity. Results from excitotoxicity model in SH-SY5Y cells suggest that activation of EP3 receptor deteriorates Glutamate-induced apoptosis by inactivating PKA through Gi activation, followed by activation of caspases with modulation of Bcl-2. Thus EP3 receptor may have the key role in neuronal apoptosis after brain ischemia and also in PD.
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