Genes in the GABA Pathway Increase in the Lateral Thalamus of Sprague-Dawley Rats During the Proestrus/Estrus Phase.
Genes in the GABA Pathway Increase in the Lateral Thalamus of Sprague-Dawley Rats During the Proestrus/Estrus Phase.
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DOI：
10.1002/jcp.25198
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发表时间：
2016-05
影响因子：
5.6
通讯作者：
Kramer PR
中科院分区：
文献类型：
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作者：
Umorin M;Stinson C;Bellinger LL;Kramer PR
在发情周期中，由于雌二醇浓度的变化，疼痛会发生变化，但引起这种变化的机制尚不清楚。由于丘脑是重要的疼痛控制，基因表达的外侧丘脑（腹后内侧，腹后外侧，网状丘脑核）在发情周期的不同阶段进行了筛选。采用实时荧光定量PCR和酶联免疫吸附试验（ELISA）分析大鼠动情周期不同阶段基因表达的变化，采用放射免疫分析（RIA）测定大鼠动情周期不同阶段血浆雌二醇水平。结果表明，当血浆雌二醇水平升高时，外侧丘脑谷氨酸脱羧酶1和2（GAD 1，GAD 2）、GABA（A）受体相关蛋白样1（GABARAPL 1）和囊泡GABA转运体（VGAT）的RNA和蛋白表达均显著增加。在发情周期的发情前期和发情期，雌激素水平升高。雌激素受体α（ER α）共定位于丘脑细胞，丘脑灌注ER α拮抗剂可显著降低GAD 1和VGAT的转录。GAD 1、GAD 2、GABARAPL 1和VGAT已经显示出影响神经元反应，这表明在动情周期期间疼痛的调节可以部分地依赖于通过雌二醇诱导的丘脑基因表达的变化。
Pain can vary over the estrous cycle as a result of changes in estradiol concentration but the mechanism causing this variation is unclear. Because the thalamus is important in pain control, gene expression in the lateral thalamus (ventral posteromedial, ventral posterolateral, reticular thalamic nuclei) was screened at different phases of the estrous cycle. Gene expression changes in Sprague-Dawley rats were further analyzed by real-time PCR and ELISA and plasma estradiol levels were measured by RIAs at different phases of the estrous cycle. Our results indicated that both the RNA and protein expression of glutamate decarboxylase 1 and 2 (GAD1, GAD2), GABA(A) receptor-associated protein like 1 (GABARAPL1) and vesicular GABA transporter (VGAT) significantly increased in the lateral thalamus when plasma estradiol levels were elevated. Estradiol levels were elevated during the proestrus and estrus phases of the estrous cycle. Estrogen receptor α (ERα) was observed to be co-localized in thalamic cells and thalamic infusion of an ERα antagonist significantly reduced GAD1 and VGAT transcript. GAD1, GAD2 GABARAPL1 and VGAT have been shown to effect neuronal responses suggesting that modulation of pain during the estrous cycle can be dependent, in part, through estradiol induced changes in thalamic gene expression.