| Budget Amount *help |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
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| Research Abstract |
We have demonstrated(1) hippocampal synthesis of estrogen, androgen, corticosterone, and(2) rapid synaptic modulation by these brain steroids.<Synthesis> We showed expression as well as neuronal/synaptic localization of essential enzymes(mRNA and protein) in the adult male rat hippocampus. Mass-spectrometric analysis demonstrated that exact levels of estradiol(E2), testosterone(T), dihydrotestosterone(DHT) were 8 nM, 18 nM and 7 nM, respectively, which were much higher than their levels in plasma. Male hippocampal levels of E2, and T were higher than those of female. Corticosterone level was 7 nM which was determined in the hippocampus of adrenalectomized rats.<Synaptic Modulation> Estradiol(E2)-induced rapid modulation(within 2 h) was demonstrated by analysis of spinogenesis and long-term potentiation(LTP) of adult male rat hippocampal slices. LTP analysis showed that 1 nM estradiol perfusion completely rescued the 1μM corticosterone-induced suppression of LTP. Synaptically localized ERαand GR are involved in these rapid effects. Analysis of dendritic spines was performed for single pyramidal neurons in the hippocampal slices. The density of spines and their head diameters were obtained by mathematical and automated software Spiso-3D which identifies spines by calculating geometrical parameters. E2 at 1 nM rapidly increased the density of spines via pathways of synaptic ERα→PKA and PKC→MAPK→actin polymerization→new spine. Both T and DHT also increased the density of spines. MAPK, PKA and PKC were also involved in these spinogenesis processes.
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