NEUROPATHOLOGIC CORRELATES OF NAA CHANGES TO CREATINE RATIO IN MACAQUE BRAIN

猕猴大脑中 NAA 变化与肌酸比率的神经病理学相关性

• 批准号: 7349116
• 负责人: M LENTZ
• 金额: $ 6.54万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349116
• 关键词: NEUROPATHOLOGIC; CORRELATES; NAA; CHANGES; CREATINE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PURPOSE: To elucidate the neuropathologic basis of transient changes in the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the primate brain by using a simian immunodeficiency virus (SIV)¿infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome. MATERIALS AND METHODS: This study was approved by the Massachusetts General Hospital Subcommittee on Research and Animal Care and the IACUC of Harvard University. Rhesus macaques infected with SIV were evaluated during the 1st month of infection. A total of 11 animals were studied, including four control animals, three animals sacrificed 12 days after infection, three animals sacrificed 14 days after infection, and one animal sacrificed 28 days after infection. All animals underwent in vivo proton (1H) magnetic resonance (MR) spectroscopy, and postmortem frontal lobe tissue was investigated by using high-spectral-resolution 1H MR spectroscopy of brain extracts. In addition, quantitative neuropathologic analyses were performed. Stereologic analysis was performed to determine neuronal counts, and immunohistochemical analysis was performed to analyze three neuronal markers: synaptophysin, microtubule-associated protein 2 (MAP2), and calbindin. Analysis of variance (ANOVA) was used to determine substantial changes in neuropathologic and MR spectroscopic markers. Spearman rank correlations were calculated between plasma viral load and neuropathologic and spectroscopic markers. RESULTS: During acute infection with SIV, the macaque brain exhibited significant changes in NAA/Cr (P .02, ANOVA) and synaptophysin (P .013, ANOVA). There was no significant change in the concentration of Cr. No significant changes were found in neuronal counts or other immunohistochemical neuronal markers. With the Spearman rank test, a significant direct correlation was detected between synaptophysin and ex vivo NAA/Cr (rs 0.72, P .013). No correlation between NAA/Cr and neuronal counts, calbindin, or MAP2 was found. CONCLUSION: NAA/Cr is a sensitive marker of neuronal injury, not necessarily neuronal loss, and best correlates with synaptophysin, a marker of synaptodendritic dysfunction.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。目得：通过使用猴免疫缺陷病毒（SIV）感染的获得性免疫缺陷综合征神经学表现的猕猴模型，阐明灵长类动物脑中N-乙酰天冬氨酸（NAA）与肌酸（Cr）比值一过性变化的神经病理学基础。材料和方法：本研究获得了马萨诸塞州总医院研究和动物护理小组委员会以及哈佛大学IACUC的批准。在感染SIV的第1个月期间评价感染SIV的恒河猴。共研究了11只动物，包括4只对照动物、3只感染后12天处死的动物、3只感染后14天处死的动物和1只感染后28天处死的动物。所有动物进行了体内质子（1H）磁共振（MR）光谱，和死后额叶组织进行了研究，通过使用高光谱分辨率1H MR光谱的脑提取物。此外，还进行了定量神经病理学分析。进行体视学分析以确定神经元计数，并进行免疫组织化学分析以分析三种神经元标记物：突触素、微管相关蛋白2（MAP 2）和钙结合蛋白。方差分析（ANOVA）用于确定神经病理学和MR光谱标记物的实质性变化。计算血浆病毒载量与神经病理学和光谱学标志物之间的斯皮尔曼等级相关性。研究结果：SIV急性感染时，猕猴脑内NAA/Cr（P0.02，ANOVA）和突触素（P0.013，ANOVA）均发生显著变化. Cr浓度无明显变化。在神经元计数或其他免疫组织化学神经元标记物中未发现显著变化。通过斯皮尔曼秩和检验，检测到突触素与离体NAA/Cr之间存在显著的直接相关性（rs 0.72，P 0.013）。NAA/Cr和神经元计数，钙结合蛋白，或MAP 2之间没有相关性founding. CONCLUSION：NAA/Cr是一个敏感的神经元损伤的标志物，不一定是神经元的损失，最好的相关性与突触素，突触树突功能障碍的标志物。