| Budget Amount *help |
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2006: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2005: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2004: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2003: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Research Abstract |
After maturation of the brain, neural progenitor cells reside at the subventricular zone, persistently generating newborn immature neurons for the olfactory bulb. It had been known that status epilepticus and cerebral ischemia stimulate persistent neurogenesis in the adult brain, but both conditions cause neuronal damage. Spreading depression is a common epiphenomenon of these neurogenesis-stimulating conditions. We analyzed the effect of spreading depression on persistent neurogenesis at the subventricular zone of the lateral ventricle, and the spatiotemporal distribution of cells exhibiting immunohistochemical markers for divided and early committed neurons (new neurons) in the ipsilateral cerebral hemisphere in adult rats. Spreading depression was induced by intra-cortical micro-infusion of KCl for 48 hours. After induction of spreading depression, the density of mitotic cells, divided cells, and new neurons in the subventricular zone increased at days 1 to 3, days 3 to 6, and day 6
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, respectively. The divided cell density in the rostral migratory stream and the stream size increased at day 12. Vehicle (saline) infusion, or induction of spreading depression for 4 hours only did not increase the divided cell density, but the latter increased new neuron density in the subventricular zone. Double-labeled new neuron-like cells also appeared in the caudate putamen or cortex in ectopic fashion at day 3, with dramatic increases at days 6 and 12. Administration of the NMDA receptor antagonist, MK-801, which inhibits the propagation of spreading depression, abolished the increase in new neurons in the SVZ and the appearance of ectopic new neuron-like cells following 48-h KCL infusion. There was no neuronal damage, as evidenced by mature neuron density, neurite density, and apoptotic cell appearance following spreading depression for 48 hours. The essentially safe stimulation, spreading depression, has the potential to stimulate persistent neurogenesis, or to produce ectopic new neuron-like immature cells in the adult brain. Less
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