Department of Endocrinology, Pathophysiology and Applied Biology-Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
J Mol Neurosci. 2012 Jan;46(1):177-83. doi: 10.1007/s12031-011-9570-y. Epub 2011 Jun 14.
An important link between neuroactive steroids and neurodegenerative disorders has recently been suggested. Indeed, in several neurodegenerative experimental models the levels of neuroactive steroids are affected and their administration exerts neuroprotective effects. However, scarce information has so far been obtained on the neuroactive steroid levels present in Parkinson's disease. To this aim, using an experimental model of loss of nigrostriatal dopaminergic neurons obtained by stereotaxic injection of the neurotoxin 6-hydroxydopamine (6-OHDA), we evaluated by liquid chromatography tandem mass spectrometry the levels of several neuroactive steroids in the striatum and cerebral cortex of 6-OHDA-lesioned male rats. Among the neuroactive steroid levels assessed (i.e., pregnenolone, progesterone, dihydroprogesterone, tetrahydroprogesterone, isopregnanolone, testosterone, dihydrotestosterone, 3α-diol, dehydroepiandrosterone, 17α-estradiol, and 17β-estradiol), we observed a significant decrease of pregnenolone in the striatum. A similar effect was also observed on the levels of dihydroprogesterone present in this cerebral area and also in the cerebral cortex. Interestingly, an increase of isopregnanolone also occurred in the striatum and in the cerebral cortex. Altogether, these results suggesting that progesterone metabolism is affected in an experimental model of Parkinson's disease further highlight the link between neuroactive steroids and the neurodegenerative diseases.
神经活性甾体与神经退行性疾病之间存在着重要的联系，这一点最近得到了证实。事实上，在几种神经退行性实验模型中，神经活性甾体的水平受到了影响，并且它们的给药表现出了神经保护作用。然而，目前关于帕金森病中存在的神经活性甾体水平的信息还很有限。为此，我们使用立体定向注射神经毒素 6-羟多巴胺（6-OHDA）获得的黑质纹状体多巴胺能神经元丧失的实验模型，通过液相色谱串联质谱法评估了 6-OHDA 损伤雄性大鼠纹状体和大脑皮层中几种神经活性甾体的水平。在所评估的神经活性甾体水平中（即孕烯醇酮、孕酮、二氢孕酮、四氢孕酮、异孕烯醇酮、睾酮、二氢睾酮、3α-二醇、脱氢表雄酮、17α-雌二醇和 17β-雌二醇），我们观察到纹状体中孕烯醇酮的含量显著降低。在该脑区和大脑皮层中，二氢孕酮的水平也观察到了类似的影响。有趣的是，异孕烯醇酮在纹状体和大脑皮层中的含量也增加了。总的来说，这些结果表明，在帕金森病的实验模型中，孕酮代谢受到了影响，进一步强调了神经活性甾体与神经退行性疾病之间的联系。
