Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Outline of Final Research Achievements |
Parkinson's disease (PD) is characterized by a selective loss of dopaminergic neurons in the substantia nigra in the brain. This study demonstrates a unique mechanism of nigral dopaminergic degeneration, in which rapid intracellular Zn2+dysregulation via reactive oxygen species (ROS) production causes PD in rats, which is induced by paraquart (PQ) and 6-hydroxydopamine (6-OHDA). ROS produced with PQ and 6-OHDA, which is retrogradely transported to presynaptic glutamatergic neuron terminals, activate TRPM2 cation channels and increase glutamate release, resulting in intracellular Zn2+ dysregulation in postsynaptic nigral dopaminergic neurons via rapid extracellular Zn2+ influx via AMPA receptor activation.
|