13C SPECTROSCOPY

13C 光谱

• 批准号: 6947423
• 负责人: BRIAN David ROSS
• 金额: $ 23.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6947423
• 关键词: AIDS /HIV neuropathy; HIV infections; bioenergetics; brain metabolism; carbon; comorbidity; drug abuse; glutamates; human subject; methamphetamine; neural transmission; neurophysiology; neurotransmitter metabolism; patient oriented research; spectrometry; stable isotope

This is a revised application for Project by Ross. Human immunodeficiency virus (HIV) and methamphetamine (METH) abuse are associated with cerebral injury. Studies utilizing proton magnetic resonance (MR) spectroscopy in abstinent METH users and HIV+ patients have revealed reduced levels of N-acetylaspartate which may be indicative of neuronal injury or death. However, the mechanism of injury is not well understood. Carbon-13 (13C) MR spectroscopy allows for in vivo measurements of important metabolic processes that may reveal the complex mechanisms of damage. To track metabolism, a ISC-labeled substrate is infused and 13C label incorporation into intermediaries provides information on metabolic pathways. One such pathway is the neuronal tricarboxylic acid cycle (VtcaN), which is a measure of energy metabolism. In addition, glutamate-glutamine cycling (Vgln) can be quantified, providing an estimate of the glutamate neurotransmission rate. In this study, 13C MR spectroscopy will be performed during an intravenous infusion of D-glucose-1-13C to study the effects of METH+ and HIV on Vgln and VtcaN. Twenty HIV+/METH+, 20 HIV+/METH-, 20 HIV-/METH+, and 20 HIV-/METH- healthy controls will be enrolled. HIV+/METH- participants are expected to display decreased Vgln and increased VtcaN, which may be indicative of excessive glutamate neurotransmission and increased glutamate synthesis, respectively. HIV- /METH+ will show increased Vgln and decreased VtcaN reflecting a neuroadaptive response to previous heavy METH use. HIV+/METH+ are expected to have similar metabolic rate profiles as HIV+/METH- because the changes related to HIV are predicted to be of greater magnitude than those due to METH. VtcaN and Vgln will be related to measures of neurocognitive and neuromotor function. Additionally, FMRI brain response and cerebrospinal fluid markers of astrocyte and neuron function will be related to 13C spectroscopy metabolic rates.

这是 Ross 对 Project 的修改后的应用程序。人类免疫缺陷病毒（HIV）和甲基苯丙胺（METH）滥用与脑损伤有关。利用质子磁共振 (MR) 光谱对戒毒者和 HIV 阳性患者进行的研究表明，N-乙酰天冬氨酸水平降低，这可能表明神经元损伤或死亡。然而，损伤机制尚不清楚。碳 13 (13C) 磁共振波谱可以对重要的代谢过程进行体内测量，从而揭示复杂的损伤机制。为了追踪代谢，注入 ISC 标记的底物，并将 13C 标记掺入中间体中，提供代谢信息 途径。其中一个途径是神经元三羧酸循环（VtcaN），它是能量代谢的衡量标准。此外，还可以量化谷氨酸-谷氨酰胺循环 (Vgln)，从而提供谷氨酸神经传递速率的估计。在本研究中，将在静脉输注 D-glucose-1-13C 期间进行 13C MR 波谱分析，以研究 METH+ 和 HIV 对 Vgln 和 VtcaN 的影响。将招募 20 名 HIV+/METH+、20 名 HIV+/METH-、20 名 HIV-/METH+ 和 20 名 HIV-/METH- 健康对照。 HIV+/METH- 参与者预计会表现出 Vgln 下降和 VtcaN 增加，这可能分别表明谷氨酸神经传递过多和谷氨酸合成增加。艾滋病病毒- /METH+ 将显示 Vgln 增加和 VtcaN 减少，反映了对之前大量使用 METH 的神经适应性反应。 HIV+/METH+ 预计具有与 HIV+/METH- 类似的代谢率分布，因为与 HIV 相关的变化预计比 METH 引起的变化幅度更大。 VtcaN 和 Vgln 将与神经认知和神经运动功能的测量相关。此外，FMRI 大脑反应以及星形胶质细胞和神经元功能的脑脊液标记物将与 13C 光谱代谢率相关。