Estradiol Rapidly Rescues Synaptic Transmission from Corticosterone-induced Suppression via Synaptic/Extranuclear Steroid Receptors in the Hippocampus
Estradiol Rapidly Rescues Synaptic Transmission from Corticosterone-induced Suppression via Synaptic/Extranuclear Steroid Receptors in the Hippocampus
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DOI：
10.1093/cercor/bhr164
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发表时间：
2012-04-01
期刊：
影响因子：
3.7
通讯作者：
Kawato, Suguru
中科院分区：
文献类型：
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作者：
Ooishi, Yuuki;Mukai, Hideo;Kawato, Suguru
我们研究了雌二醇对皮质酮（CORT）诱导的突触传递抑制的快速保护作用。1 μ M CORT对CA3-CA1突触长期增强（LTP）的快速抑制通过1 nM雌二醇共灌注消除。利用n -甲基-d -天冬氨酸（NMDA）受体衍生的场兴奋性突触后电位（NMDA- r- fepsp）分析了这些事件的发生机制。雌二醇可消除cort诱导的NMDA-R-fEPSP斜率抑制。钙调磷酸酶抑制剂可消除这种cort诱导的抑制作用，而雌二醇对cort诱导的抑制作用可被丝裂原活化蛋白激酶抑制剂抑制。糖皮质激素受体（GR）拮抗剂可消除cort诱导的LTP和NMDA-R-fEPSP斜率的抑制，雌二醇对这些过程的恢复作用可被雌激素受体α (ER α)和ER β激动剂模拟。综上所述，雌二醇可迅速将LTP和NMDA-R-fEPSP从cort诱导的抑制中解救出来。GR ->钙调磷酸酶通路参与了这些抑制作用。雌二醇的拯救作用是通过ER α或ER β -> MAP激酶途径驱动的。突触/核外GR、ER α和ER β可能参与了这些快速事件。质谱分析确定用于电生理测量的急性海马切片含有0.48 nM雌二醇，比外源性应用1 nM雌二醇少。体内生理水平8 nM雌二醇可保护完整海马免受急性应激性神经抑制。
We investigated rapid protection effect by estradiol on corticosterone (CORT)-induced suppression of synaptic transmission. Rapid suppression by 1 mu M CORT of long-term potentiation (LTP) at CA3-CA1 synapses was abolished via coperfusion of 1 nM estradiol. N-methyl-D-aspartate (NMDA) receptor-derived field excitatory postsynaptic potential (NMDA-R-fEPSP) was used to analyze the mechanisms of these events. Estradiol abolished CORT-induced suppression of NMDA-R-fEPSP slope. This CORT-induced suppression was abolished by calcineurin inhibitor, and the rescue effect by estradiol on the CORT-induced suppression was inhibited by mitogen-activated protein (MAP) kinase inhibitor. The CORT-induced suppressions of LTP and NMDA-R-fEPSP slope were abolished by glucocorticoid receptor (GR) antagonist, and the restorative effects by estradiol on these processes were mimicked by estrogen receptor alpha (ER alpha) and ER beta agonists. Taken together, estradiol rapidly rescued LTP and NMDA-R-fEPSP slope from CORT-induced suppressions. A GR -> calcineurin pathway is involved in these suppressive effects. The rescue effects by estradiol are driven via ER alpha or ER beta -> MAP kinase pathway. Synaptic/extranuclear GR, ER alpha, and ER beta probably participate in these rapid events. Mass-spectrometric analysis determined that acute hippocampal slices used for electrophysiological measurements contained 0.48 nM estradiol less than exogenously applied 1 nM. In vivo physiological level of 8 nM estradiol could protect the intact hippocampus against acute stress-induced neural suppression.