Modulation of synaptic plasticity in the hippocampus by hippocampus-derived estrogen and androgen

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• 作者：Yuuki Ooishi^a ; Suguru Kawato^a ; ^b ; ^c ; ^d ; ^{kawato@phys.c.u-tokyo.ac.jp} ; ^{kawato@bio.c.u-tokyo.ac.jp} ; Yasushi Hojo^a ; ^b ; ^c ; Yusuke Hatanaka^a ; Shimpei Higo^a ; Gen Murakami^a ; ^c ; Yoshimasa Komatsuzaki^a ; Mari Ogiue-Ikeda^a ; ^d ; Tetsuya Kimoto^a ; Hideo Mukai^a ; ^b ; ^c
• 关键词：ACSF ; artificial cerebrospinal fluid ; AMPA ; 伪-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ; CNQX ; 6-cyano-7-nitroquinoxaline-2 ; 3-dione ; DHEA ; dehydroepiandrosterone ; DPN ; diarylpropionitrile ; DHT ; dihydrotestosterone ; E2 ; 17尾-estradiol ; E1 ; estron
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2012
• 期刊代码：172_09600760
• 类别：med
• 出版时间：August, 2012
• 卷：131
• 期：1-2
• 页码：37-51
• 文件大小：2324 K

摘要

The hippocampus synthesizes estrogen and androgen in addition to the circulating sex steroids. Synaptic modulation by hippocampus-derived estrogen or androgen is essential to maintain healthy memory processes. Rapid actions (1-2 h) of 17尾-estradiol (17尾-E2) occur via synapse-localized receptors (ER伪 or ER尾), while slow genomic E2 actions (6-48 h) occur via classical nuclear receptors (ER伪 or ER尾). The long-term potentiation (LTP), induced by strong tetanus or theta-burst stimulation, is not further enhanced by E2 perfusion in adult rats. Interestingly, E2 perfusion can rescue corticosterone (stress hormone)-induced suppression of LTP. The long-term depression is modulated rapidly by E2 perfusion. Elevation of the E2 concentration changes rapidly the density and head structure of spines in neurons. ER伪, but not ER尾, drives this enhancement of spinogenesis. Kinase networks are involved downstream of ER伪. Testosterone (T) or dihydrotestosterone (DHT) also rapidly modulates spinogenesis. Newly developed Spiso-3D mathematical analysis is used to distinguish these complex effects by sex steroids and kinases.

It has been doubted that the level of hippocampus-derived estrogen and androgen may not be high enough to modulate synaptic plasticity. Determination of the accurate concentration of E2, T or DHT in the hippocampus is enabled by mass-spectrometric analysis in combination with new steroid-derivatization methods. The E2 level in the hippocampus is approximately 8 nM for the male and 0.5-2 nM for the female, which is much higher than that in circulation. The level of T and DHT is also higher than that in circulation. Taken together, hippocampus-derived E2, T, and DHT play a major role in modulation of synaptic plasticity.