MEASUREMENTS AND METABOLISM OF NEUROSTEROIDS IN THE CENT

中心神经类固醇的测量和代谢

• 批准号: 6431366
• 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/6431366
• 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. Neurosteroids such as 5a-pregnane-3a-ol-20-one (5a,3a-THP or Allopregnanolone) and 5a-pregnane-3a,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 central nervous system by ethanol may be one of the underlying mechanisms for stress observed in human alcoholics especially during withdrawal. The GC/MS-NCI technique that we previousely established for the measurements of trace levels of neurosteroids in human cerebro spinal fluids (CSF) has been improved to include the analysis of progesterone and dihydroprogesterone, and extended to the analysis of human and rat plasma samples in this period. We were able to quantitate pregnenolone, 5a,3a-, 5b,3a-, 5a,3b-THP, androsterone and dihydrotestosterone, dihydroprogesterone and progesterone in those samples. Using this technique, we participated in the development of a pseudopregnancy model of catamenial epilepsy by NINDS investigators. Investigations on the effect of progesterone metabolism on post-partum depression are now in progress in collaboration with NIMH.

这项研究的主要目的是确定乙醇对中枢神经系统中神经类固醇代谢的影响。神经类固醇（例如5A-Pregnane-3a-ol-20-One（5a，3a-thp或Allopregnanolone）和5A-Pregnane-3A，21-二醇-20-ONE（THDOC）已显示可调节GABA/Benzodiazepine结合位点和锻炼抗焦点​​抗焦点和催眠型和催眠效果。 通过乙醇对中枢神经系统中这些神经类固醇的调节可能是人类酒精中毒中观察到的压力的潜在机制之一，尤其是在戒断期间。 我们先前确定的GC/MS-NCI技术已改进了人类脑脊髓液（CSF）的痕量水平神经类固醇（CSF）的痕量水平，以包括孕酮和二氢丙酮的分析，并扩展到此期间人类和大鼠血浆样品的分析。 我们能够定量孕妇，5A，3A-，5B，3A-，5A，3B-THP，雄激素，二氢睾丸激素，二氢雌激素和孕酮中的孕酮。 使用这种技术，我们参与了Ninds研究者的神经癫痫的伪孕模型的开发。 对孕酮代谢对产后抑郁症的影响的研究正在与NIMH合作进行。