Estradiol rapidly modulates spinogenesis in hippocampal dentate gyrus: Involvement of kinase networks
Estradiol rapidly modulates spinogenesis in hippocampal dentate gyrus: Involvement of kinase networks
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DOI：
10.1016/j.yhbeh.2015.06.008
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发表时间：
2015-08-01
影响因子：
3.5
通讯作者：
Kawato, Suguru
中科院分区：
文献类型：
--
作者：
Hojo, Yasushi;Munetomo, Arisa;Kawato, Suguru
E2在海马和性腺内局部合成。E2对海马突触可塑性的快速调节对于突触调节至关重要。然而，通过突触雌激素受体（ER）及其下游信号传导的调节的分子机制在齿状回（DG）中在很大程度上是未知的。我们研究了E2诱导的调制雄性成年大鼠海马脑片的树突棘成像荧光黄注射DG颗粒细胞。用1 nM E2处理使棘的密度在2小时内增加约1.4倍。棘头直径分析表明，中头棘（0.4-0.5 μ m）密度显著增加。阻断Erk MAPK、PICA、PKC和LIMK可抑制E2诱导的棘密度增加。激酶抑制剂的这些抑制作用不是非特异性的，因为GSK-3 β拮抗剂不抑制E2诱导的棘增加。ER拮抗剂ICI 182，780也阻断E2诱导的棘增加。总之，这些结果表明，E2通过突触ER驱动的激酶网络快速增加棘的密度。(C)2015 Elsevier Inc. All rights reserved.
Estradiol (E2) is locally synthesized within the hippocampus and the gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential for synaptic regulation. The molecular mechanisms of modulation through the synaptic estrogen receptor (ER) and its downstream signaling, however, are largely unknown in the dentate gyrus (DG). We investigated the E2-induced modulation of dendritic spines in male adult rat hippocampal slices by imaging Lucifer Yellow-injected DG granule cells. Treatments with 1 nM E2 increased the density of spines by approximately 1.4-fold within 2 h. Spine head diameter analysis showed that the density of middle-head spines (0.4-0.5 mu m) was significantly increased. The E2-induced spine density increase was suppressed by blocking Erk MAPK, PICA, PKC and LIMK. These suppressive effects by kinase inhibitors are not non-specific ones because the GSK-3 beta antagonist did not inhibit E2-induced spine increase. The ER antagonist ICI 182,780 also blocked the E2-induced spine increase. Taken together, these results suggest that E2 rapidly increases the density of spines through kinase networks that are driven by synaptic ER. (C) 2015 Elsevier Inc. All rights reserved.