Estrogen-priming can enhance progesterone's anti-seizure effects in part by increasing hippocampal levels of allopregnanolone
Estrogen-priming can enhance progesterone's anti-seizure effects in part by increasing hippocampal levels of allopregnanolone
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DOI：
10.1016/j.pbb.2005.06.016
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发表时间：
2005-08-01
影响因子：
3.6
通讯作者：
Rhodes, ME
中科院分区：
文献类型：
--
作者：
Frye, CA;Rhodes, ME
雌激素可以是促惊厥的，而孕酮及其代谢物别孕烯醇酮通常具有抗癫痫作用。我们研究了雌激素引发是否也有抗癫痫发作的作用，通过改变孕酮的代谢，别孕烯醇酮，或脑源性神经营养因子（BDNF）的水平，在海马。两个实验研究了不同的雌激素引发方案（实验1-10 μ g;实验2-2 μ g）对戊四唑（PTZ）诱导的癫痫发作以及血浆和海马中雌激素、孕酮和别孕烯醇酮水平的影响。在实验1中，卵巢切除（ovx）的大鼠在0小时给予芝麻油载体或10 μ g 17 β-雌激素。44小时后，给予孕酮（500 μ g，SC）或溶媒。在第47小时，给予PTZ（70 mg/kg IP）。对于实验2，除了在0和24小时给ovx大鼠施用载体或2 μ g 17 β-雌二醇外，使用类似的方案。孕激素，单独或与10或2微克雌激素引发，往往会增加潜伏期，并显着减少，强直性发作和海马和血浆中孕激素水平升高的数量。两微克而不是10微克的雌激素单独具有抗癫痫作用，并增加海马体中的别孕烯醇酮水平。海马中的BDNF水平通过雌激素引发而增加，但通过孕酮施用而减少。因此，雌激素可能通过增强别孕烯醇酮的合成而具有抗癫痫作用。(c)2005年爱思唯尔公司All rights reserved.
Estrogen can be proconvulsant, while progesterone and its metabolite allopregnanolone typically have anti-seizure effects. We investigated whether estrogen-priming also has anti-seizure effects by altering progesterone's metabolism to allopregnanolone, or levels of brain-derived neurotrophic factor (BDNF), in the hippocampus. Two experiments investigated effects of different estrogen-priming regimen (Experiment 1-10 mu g; Experiment 2-2 mu g) on pentylenetetrazole (PTZ)-induced seizures and levels of estrogen, progesterone and allopregnanolone in plasma and hippocampus. In Experiment 1, ovariectomized (ovx) rats were administered sesame oil vehicle or 10 mu g 17 beta-estrogen at hour 0. Forty-four hours later, progesterone (500 mu g;, SC) or vehicle was administered. At hour 47, PTZ (70 mg/kg IP) was administered. For Experiment 2, a similar protocol was used except that ovx rats were administered vehicle or 2 mu g 17 beta-estradiol at hours 0 and 24. Progesterone, alone or in conjunction with either 10 or 2 mu g estrogen-priming, tended to increase the latency to, and significantly reduced the number of, tonic seizures and elevated levels of progestins in hippocampus and plasma. Two, but not 10, micrograms of estrogen alone had anti-seizure effects and increased levels of allopregnanolone in the hippocampus. BDNF levels in the hippocampus were increased by estrogen-priming, but reduced by progesterone administration. Thus, estrogen may have anti-seizure effects by enhancing fort-nation of allopregnanolone. (c) 2005 Elsevier Inc. All rights reserved.