| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Research Abstract |
It is generally believed that reduction of brain derived neurotrophic factor (BDNF) in the hippocampus causes decreased neurogenesis and memory disturbance. We, therefore, searched for BDNF-enhancing reagents in the dentate gyrus of the rat hippocampus and investigated effects of a high level of BDNF on granule cell precursors. In addition, to clarify the controlling mechanisms of BDNF synthesis, we examined intracellular signaling pathways that are activated by drugs.
1)Riluzole, a blocker of voltage-dependent sodium channel, enhanced BDNF levels in the rat hippocampus. Repeated injection of riluzole kept a high level of BDNF in the hippocampus and increased the number of granule cell precursors. Most of the newly produced cells differentiated to neurons (90%).
2)It was demonstrated that the increase of precursor cell number is caused by promoted cell proliferation and that BDNF is necessary, but not sufficient, for such proliferation.
3)Riluzole injection enhanced markedly, slightly, and hardly phosphorylation of p38 MAP kinase, ERK1, and Akt, respectively.
4)SB203580, an inhibitor of p38 MAP kinase, decreased levels of phosphorylated kinase and BDNF in the rat hippocampus. On the contrary, anisomycin, an activator of p38 MAP kinase, increased them.
Thus, we concluded that the activation of both p38 MAP kinase and ERK1 is necessary to induce BDNF synthesis.
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