Background: Neurosteroids modulate epileptic activity by interacting with the γ-aminobutyric acid type A receptor, but their brain levels are still undetermined. Objectives: We aimed to establish levels of neurosteroids in the neocortex and hippocampus by liquid chromatography–mass spectrometry in epileptic rats. Methods: Kainic acid-treated rats were continuously monitored up to 9 weeks to determine the seizure frequency by video electrocorticography (n=23), and compared to age-matched controls monitored in the same manner (n=11). Results: A reduction in allopregnanolone (-50%; p<0.05, Mann-Whitney test) and pregnanolone levels (-64%; p<0.01) was found in the hippocampus, whereas pregnenolone sulfate, pregnenolone, progesterone, and 5α-dihydroprogesterone were nonsignificantly reduced. No changes were found in the neocortex. Moreover, allopregnanolone (but not pregnanolone) levels were positively correlated with the seizure frequency (r2=0.4606, p<0.01). Conclusions: These findings indicate a selective reduction in hippocampal levels of 3α-reduced neurosteroids. This reduction was partially mitigated by seizures in the case of allopregnanolone.


中文翻译：

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癫痫大鼠海马中的 Allopregnanolone 和 pregnanolone 减少，但只有 allopregnanolone 与癫痫发作频率相关。

背景：神经类固醇通过与 γ-氨基丁酸 A 型受体相互作用来调节癫痫活动，但它们的大脑水平仍未确定。目的：我们旨在通过液相色谱-质谱法确定癫痫大鼠新皮质和海马中神经类固醇的水平。方法：连续监测海藻酸处理的大鼠长达 9 周，以通过视频皮层电图 (n=23) 确定癫痫发作频率，并与以相同方式监测的年龄匹配的对照组 (n=11) 进行比较。结果：海马中的别孕醇酮（-50%；p<0.05，Mann-Whitney 检验）和孕醇酮水平（-64%；p<0.01）降低，而硫酸孕烯醇酮、孕烯醇酮、孕酮和 5α-二氢孕酮没有显着减少。在新皮质中没有发现任何变化。而且，allopregnanolone（但不是 pregnanolone）水平与癫痫发作频率呈正相关（r2=0.4606，p<0.01）。结论：这些发现表明 3α 减少的神经类固醇的海马水平选择性降低。在别孕醇酮的情况下，癫痫发作部分缓解了这种减少。