2011 Fiscal Year Final Research Report
Modulation of Hippocampal Synaptic Plasticity by Brain Steroid Hormones
| Project/Area Number |
21370064
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KAWATO Suguru 東京大学, 大学院・総合文化研究科, 教授 (50169736)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 脳神経系の情報処理 / 神経内分泌学 |
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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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[Journal Article] Endogenous Synthesis of Corticosteroids in the Hippocampus2011
Author(s)
Higo S, . Hojo Y., Ishii H, Komatsuzaki Y., Ooishi Y., Murakami G., Mukai H., Yamazaki T., Nakahara D., Anna B, Kimoto T., and Kawato S
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Journal Title
PLoS ONE
Volume: 6
Pages: e21631
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[Journal Article] Hippocampal synthesis of sex steroids and corticosteroids : essential for modulation of synaptic plasticity2011
Author(s)
Hojo Y, Higo S, Kawato S, Hatanaka Y, Ooishi Y, Murakami G, Ishii H, Komatsuzaki Y, Ogiue-Ikeda M, Mukai H, and Kimoto T
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Journal Title
Front Neuroendocrine Science
Volume: Vol2
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[Journal Article] Comparison between Hippocampus-Synthesized and Circulation-Derived Sex Steroids in the Hippocampus2009
Author(s)
Hojo Y., Higo S., Ishii H., Ooishi Y., Mukai H., Murakami G., Kominami T., Kimoto T., Honma S., Poirier D., and Kawato S
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Journal Title
Endocrinology
Volume: 150
Pages: 5106-5112
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[Presentation] Rapid modulation of synaptic plasticity by hippocampal-derived sex-steroids2009
Author(s)
Mukai, H., Hatanaka, Y., Sato, R., Ooishi, Y., Ogiue-Ikeda, M., Hojo, Y., Kominami, S., Kawato, S
Organizer
The 36th Congress of the International Union of Physiological Sciences
Place of Presentation
Kyoto
Year and Date
20090700
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