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.

这是一个修改后的应用程序项目由罗斯。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）光谱在禁欲METH用户和HIV+患者的研究表明，N-乙酰天冬氨酸水平降低，这可能是神经元损伤或死亡的指示。然而，损伤的机制还不清楚。碳-13（13 C）MR光谱允许在体内测量重要的代谢过程，可能揭示复杂的损伤机制。为了跟踪代谢，注入ISC标记的底物，13 C标记掺入中间体提供代谢信息。 途径。一种这样的途径是神经元三羧酸循环（VtcaN），其是能量代谢的量度。此外，谷氨酸-谷氨酰胺循环（Vgln）可以量化，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-葡萄糖-1-13 C期间进行13 C MR波谱分析，以研究METH+和HIV对Vgln和VtcaN的影响。将入组20例HIV+/METH+、20例HIV+/METH-、20例HIV-/METH+和20例HIV-/METH-健康对照。预计HIV+/METH-参与者将显示Vgln降低和VtcaN增加，这可能分别指示过量的谷氨酸神经传递和谷氨酸合成增加。艾滋病毒- /METH+将显示增加的Vgln和减少的VtcaN，反映对先前大量使用METH的神经适应性反应。预计HIV+/METH+与HIV+/METH-具有相似的代谢率特征，因为预计与HIV相关的变化幅度大于METH引起的变化。VtcaN和Vgln将与神经认知和神经运动功能的测量相关。此外，FMRI脑反应和星形胶质细胞和神经元功能的脑脊液标志物将与13 C光谱代谢率相关。