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.

这是罗斯（Ross）的项目修订申请。人免疫缺陷病毒（HIV）和甲基苯丙胺（甲基苯丙胺）滥用与脑损伤有关。利用戒除甲基使用者和HIV+患者中质子磁共振（MR）光谱法的研究表明，N-乙酰天冬氨酸水平降低，这可能表明神经元损伤或死亡。但是，伤害机制尚不清楚。碳13（13C）MR光谱法可以在体内测量重要的代谢过程，这些过程可能揭示了损害的复杂机制。为了跟踪新陈代谢，注入了ISC标记的底物，并将13C标签掺入中介中提供有关代谢的信息 途径。这样的途径是神经元三羧酸周期（VTCAN），它是能量代谢的量度。此外，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率的估计值。在这项研究中，将在静脉注射D-葡萄糖-1-13C静脉输注期间进行13C MR光谱法研究MECH+和HIV对VGLN和VTCAN的影响。将招募20个HIV+/METH+，20 HIV+/METH-，20 HIV-/METH+和20 HIV-/METH-HEALTOWS对照组。 HIV+/MECH-参与者预计将显示VGLN降低和VTCAN增加，这可能表明过度谷氨酸神经传递和增加谷氨酸合成。艾滋病病毒- /meth+将显示出增加的VGLN并减少VTCAN，反映了对先前重型甲基使用的神经适应反应。 HIV+/METH+的代谢率谱图与HIV+/METH-相似，因为预计与HIV相关的变化将比由于甲基甲基甲基元素的变化大。 VTCAN和VGLN将与神经认知和神经运动功能的度量有关。此外，星形胶质细胞和神经元功能的fMRI脑反应和脑脊液标记将与13C光谱代谢率有关。