An in vivo ultrahigh field 14.1 T 1H-MRS study on 6-OHDA and α-synuclein-based rat models of Parkinson's disease: GABA as an early disease marker
An in vivo ultrahigh field 14.1 T 1H-MRS study on 6-OHDA and α-synuclein-based rat models of Parkinson's disease: GABA as an early disease marker
复制标题
DOI：
10.1002/nbm.2817
复制
发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
Gruetter, R.
中科院分区：
文献类型：
--
作者：
Coune, P. G.;Craveiro, M.;Gruetter, R.
在彻底神经变性之前的临床前阶段检测帕金森病（PD）对神经保护疗法的发展至关重要，可以减少误诊患者的数量。然而，目前缺乏可靠的生物标志物阻碍了早期诊断。H-1磁共振波谱（MRS）提供了一种非侵入性的测量大脑代谢物水平，允许识别这些潜在的生物标志物。本研究的目的是利用磁共振波谱仪在14.1T磁场上研究两种不同的疾病模型大鼠纹状体代谢的变化。通过在内侧前脑束中注射6-羟基多巴胺（6-OHDA）损伤的大鼠用于模拟完全黑质纹状体病变，而基于黑质注射编码人α-突触核蛋白的腺相关病毒（AAV）载体的遗传模型用于模拟进行性神经变性和多巴胺能神经元功能障碍，从而复制更接近PD早期病理阶段的病症。在纹状体的MRS测量的6-OHDA大鼠显示，谷氨酸和N-乙酰-天冬氨酸水平显着降低，GABA水平显着增加，在同侧半球相比，对侧之一，而α-Syn过表达的大鼠表现出显着增加的GABA纹状体水平。因此，我们的结论是，MRS测量纹状体GABA水平可以允许检测早期黑质纹状体缺陷之前彻底的神经变性，因此，作为一个敏感的生物标志物的症状前PD提供了巨大的潜力。版权所有（C）2012约翰威利父子有限公司
The detection of Parkinson's disease (PD) in its preclinical stages prior to outright neurodegeneration is essential to the development of neuroprotective therapies and could reduce the number of misdiagnosed patients. However, early diagnosis is currently hampered by lack of reliable biomarkers. H-1 magnetic resonance spectroscopy (MRS) offers a noninvasive measure of brain metabolite levels that allows the identification of such potential biomarkers. This study aimed at using MRS on an ultrahigh field 14.1 T magnet to explore the striatal metabolic changes occurring in two different rat models of the disease. Rats lesioned by the injection of 6-hydroxydopamine (6-OHDA) in the medial-forebrain bundle were used to model a complete nigrostriatal lesion while a genetic model based on the nigral injection of an adeno-associated viral (AAV) vector coding for the human alpha-synuclein was used to model a progressive neurodegeneration and dopaminergic neuron dysfunction, thereby replicating conditions closer to early pathological stages of PD. MRS measurements in the striatum of the 6-OHDA rats revealed significant decreases in glutamate and N-acetyl-aspartate levels and a significant increase in GABA level in the ipsilateral hemisphere compared with the contralateral one, while the alpha Syn overexpressing rats showed a significant increase in the GABA striatal level only. Therefore, we conclude that MRS measurements of striatal GABA levels could allow for the detection of early nigrostriatal defects prior to outright neurodegeneration and, as such, offers great potential as a sensitive biomarker of presymptomatic PD. Copyright (C) 2012 John Wiley & Sons, Ltd.