1] Department of Neurology, University of Wisconsin-Madison, Medical Sciences Center, 1300 University Ave, Room 73 Bardeen, Madison, WI, USA [2] Neuroscience Training Program, University of Wisconsin-Madison, Madison, USA.
Gene Ther. 2013 Dec;20(12):1172-7. doi: 10.1038/gt.2013.47. Epub 2013 Sep 19.
Contrast agents are commonly used in combination with magnetic resonance imaging (MRI) to monitor the distribution of molecules in the brain. Recent experiments conducted in our laboratory have shown that co-infusion of recombinant Adeno-associated virus serotype 5 (rAAV5) and the MRI contrast agent gadoteridol (Gd) enhances vector transduction in the rat striatum. The goal of this study was to determine whether gadoteridol may also be used as a tool to enhance transduction efficiency of rAAV1 and rAAV5 within the rat hippocampus. We show that Gd/rAAV1-GFP but not Gd/rAAV5-GFP co-infusion results in significantly higher distribution of the transgene both in the injected hemisphere as well as in the contralateral side and adjacent areas of cortex along the injection track. We also show that Gd/rAAV1-GFP co-infusion has no deleterious effect on hippocampal function as assessed by two tests of spatial memory formation. This work indicates that Gd can be exploited as a method to increase transduction efficiency of AAV1 in the hippocampus for animal studies.
对比剂通常与磁共振成像(MRI)结合使用,以监测大脑中分子的分布。我们实验室最近的实验表明,重组腺相关病毒血清型 5(rAAV5)和 MRI 对比剂钆喷替酸葡甲胺(Gd)的共同输注增强了大鼠纹状体中的载体转导。本研究的目的是确定 Gd 是否也可作为一种工具,增强 rAAV1 和 rAAV5 在大鼠海马中的转导效率。我们发现 Gd/rAAV1-GFP 而非 Gd/rAAV5-GFP 的共同输注导致转基因在注射半球以及对侧和注射轨迹沿侧的相邻皮层区域的分布显著增加。我们还发现,Gd/rAAV1-GFP 的共同输注对海马功能没有不良影响,这可以通过两项空间记忆形成测试来评估。这项工作表明,Gd 可被用作增加 AAV1 在海马中转导效率的方法,用于动物研究。