癫痫大鼠海马中的异孕烷醇酮和孕烷醇酮减少，但只有异孕烷醇酮与癫痫发作频率相关。

Allopregnanolone and Pregnanolone Are Reduced in the Hippocampus of Epileptic Rats, but Only Allopregnanolone Correlates with Seizure Frequency.

机构信息

Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

出版信息

Neuroendocrinology. 2021;111(6):536-541. doi: 10.1159/000509093. Epub 2020 Jun 3.

DOI:10.1159/000509093

PMID:32492675

Abstract

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 neurosteroid levels 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 seizure frequency by video electrocorticography (n = 23) and compared to age-matched controls monitored in the same manner (n = 11).

RESULTS

Decreased allopregnanolone (-50%; p < 0.05, Mann-Whitney test) and pregnanolone levels (-64%; p < 0.01) were 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 seizure frequency (r2 = 0.4606, p < 0.01).

CONCLUSION

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.

摘要

背景

神经甾体通过与γ-氨基丁酸 A 型受体相互作用来调节癫痫活动，但它们在大脑中的水平仍未确定。

目的

我们旨在通过液相色谱/质谱法在癫痫大鼠中建立新皮层和海马中的神经甾体水平。

方法

用海人酸处理大鼠，通过视频脑电图连续监测 9 周，以确定癫痫发作频率（n = 23），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

在海马体中发现了去甲孕烯醇酮（-50%；p < 0.05，Mann-Whitney 检验）和孕烯醇酮水平（-64%；p < 0.01）降低，而孕烯醇酮硫酸盐、孕烯醇酮、孕酮和 5α-二氢孕酮则无明显降低。在新皮层中未发现变化。此外，去甲孕烯醇酮（而非孕烯醇酮）水平与癫痫发作频率呈正相关（r2 = 0.4606，p < 0.01）。