MEASUREMENTS AND METABOLISM OF NEUROSTEROIDS IN THE CENT

中心神经类固醇的测量和代谢

• 批准号: 6160354
• 负责人: Hee-Yong Kim
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160354
• 关键词: Primates; alcoholism /alcohol abuse; brain metabolism; cerebrospinal fluid; drug withdrawal; electrospray ionization mass spectrometry; ethanol; laboratory rat; neuroendocrine system; pregnanolone; progesterone analog; steroid hormone metabolism

The principal objective of this study is to determine the effect of ethanol on the metabolism of neurosteroids in the central nervous system (CNS). Neurosteroids such as 5alpha-pregnane-3alpha-ol-20-one (THP or Allopregnanolone) and 5alpha-pregnane-3alpha,21-diol-20-one (THDOC) have been shown to modulate the GABA/benzodiazepine binding sites and to exert anxiolytic and hypnotic effects. Modulation of these neurosteroids in the CNS by ethanol may be one of the underlying mechanisms for stress- related situations in humans, a side effect often observed in alcoholics during withdrawal. As part of a continuing effort to establish a mass spectrometric technique which has adequate sensitivity to routinely measure trace levels of neurosteroids in cerebral spinal fluid (CSF), we explored other approaches using gas chromatography mass spectrometry (GC/MS) after derivatizing neurosteroids with an electron capturing moiety. In this mode, with the exceptions of progesterone and dihydroprogesterone, various neurosteroids were detected at 1 pg level. Characterization of the level of neuroactive steroids in rat brain and plasma as well as in monkey CSF is now in progress using this method.

这项研究的主要目的是确定 中枢神经系统中神经类固醇代谢的乙醇 （CNS）。 神经类固醇，例如5alpha-pregnane-3alpha-ol-20-One（THP或 Allopregnanolone）和5Alpha-Pregnane-3alpha，21-Diol-20-One（THDOC）具有 已显示用于调节GABA/Benzodiazepine结合位点并发挥作用 抗焦虑和催眠作用。 这些神经类固醇的调节 乙醇的中枢神经系统可能是应激的潜在机制之一 人类的相关情况，在酗酒者中经常观察到这种副作用 在退出期间。 作为建立群众的持续努力的一部分 光谱技术具有足够的敏感性 测量脑脊髓液（CSF）中神经类固醇的痕量水平，我们 使用气相色谱质谱法探索了其他方法 （GC/MS）用电子捕获来衍生神经类固醇后 部分。 在这种模式下，孕酮和 二氢雌激素，在1 pg水平下检测到各种神经类固醇。 大鼠脑中神经活性类固醇水平的表征 现在使用此方法正在进行血浆以及猴子CSF。