A novel therapeutic approach for treatment of catamenial epilepsy.
A novel therapeutic approach for treatment of catamenial epilepsy.
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DOI：
10.1016/j.nbd.2017.12.009
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发表时间：
2018-03
影响因子：
6.1
通讯作者：
Kapur J
中科院分区：
文献类型：
--
作者：
Joshi S;Sun H;Rajasekaran K;Williamson J;Perez-Reyes E;Kapur J
许多患有癫痫的女性经历月经期癫痫发作加重，称为月经性癫痫。对于这种情况没有有效的治疗方法，建议由孕酮的神经甾体介导的作用引起。一个双盲，多中心，第三阶段，月经性癫痫的临床试验未能发现孕酮的有益作用。神经甾体介导的孕激素作用与月经性癫痫的关系已被广泛研究，然而，孕激素受体激活介导的作用却被忽视了。我们确定了孕激素是否通过激活孕激素受体增加海马的兴奋性传递，这可能在调节月经性癫痫发作加重中发挥作用。在一项使用大鼠月经期癫痫模型的双盲研究中，我们发现用阻断孕酮和糖皮质激素受体的RU-486治疗可显著减弱神经类固醇戒断诱导的癫痫发作。此外，孕激素处理以及内源性孕激素的上升，在动情周期增加的表达的GluA 1和GluA 2的AMPA受体亚单位在海马，并增强AMPA受体介导的突触传递的CA 1锥体神经元。孕酮诱导的AMPA受体可塑性被RU-486阻断，孕酮也不能增加孕酮受体敲除小鼠的AMPA受体表达。这些研究表明，孕激素受体激活调节AMPA受体的表达，并可能在月经性癫痫发作加重中发挥作用。
Many women with epilepsy experience perimenstrual seizure exacerbation, referred to as catamenial epilepsy. There is no effective treatment for this condition, proposed to result from withdrawal of neurosteroid-mediated effects of progesterone. A double-blind, multicenter, phase III, clinical trial of catamenial epilepsy has failed to find a beneficial effect of progesterone. The neurosteroid-mediated effects of progesterone have been extensively studied in relation to catamenial epilepsy; however, the effects mediated by progesterone receptor activation have been overlooked. We determined whether progesterone increased excitatory transmission in the hippocampus via activation of progesterone receptors, which may play a role in regulating catamenial seizure exacerbation. In a double-blind study using a rat model of catamenial epilepsy, we found that treatment with RU-486, which blocks progesterone and glucocorticoid receptors, significantly attenuated neurosteroid withdrawal-induced seizures. Furthermore, progesterone treatment as well as endogenous rise in progesterone during estrous cycle increased the expression of GluA1 and GluA2 subunits of AMPA receptors in the hippocampi, and enhanced the AMPA receptor-mediated synaptic transmission of CA1 pyramidal neurons. The progesterone-induced plasticity of AMPA receptors was blocked by RU-486 treatment and progesterone also failed to increase AMPA receptor expression in progesterone receptor knockout mice. These studies demonstrate that progesterone receptor activation regulates AMPA receptor expression and may play a role in catamenial seizure exacerbation.
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影响因子：
1.5
作者：
Hashimoto-Partyka, Minako K.;Lydon, John P.;Iruela-Arispel, M. Luisa
通讯作者：
Iruela-Arispel, M. Luisa
影响因子：
1.7
作者：
Aminmansour, Bahram;Asnaashari, Ali;Abdollahzadeh, Parisa
通讯作者：
Abdollahzadeh, Parisa
影响因子：
5.3
作者：
Fujita, Satoshi;Toyoda, Izumi;Buckmaster, Paul S.
通讯作者：
Buckmaster, Paul S.
DOI：
10.1016/0022-4731(85)90401-7
发表时间：
1985-01-01
影响因子：
4.1
作者：
GAGNE, D;PONS, M;PHILIBERT, D
通讯作者：
PHILIBERT, D
影响因子：
11.2
作者：
Janzen DM;Rosales MA;Paik DY;Lee DS;Smith DA;Witte ON;Iruela-Arispe ML;Memarzadeh S
通讯作者：
Memarzadeh S