Genotype specific age related changes in a transgenic rat model of Huntington's disease
Genotype specific age related changes in a transgenic rat model of Huntington's disease
复制标题
DOI：
10.1016/j.neuroimage.2011.07.007
复制
发表时间：
2011-10-15
期刊：
影响因子：
5.7
通讯作者：
Van der Linden, Annemie
中科院分区：
文献类型：
--
作者：
Blockx, Ines;Van Camp, Nadja;Van der Linden, Annemie
我们的目的是通过体内成像来表征转基因亨廷顿大鼠模型，并鉴定与早期和进行性疾病状态相关的敏感和可靠的生物标志物。为了做到这一点，我们进行了多模态（DTI和PET）纵向成像研究，在此期间，相同的TgHD和野生型（Wt）大鼠进行了重复扫描。令人惊讶的是，与Wt动物相比，TgHD中的相对心室体积较小，但增加更快。DTI（平均，轴向，径向扩散率）揭示了微妙的基因型特异性的老化效应，在纹状体及其周围的白色物质，已经在前驱阶段。使用F-18-FDG和F-18-Fallypride PET成像，我们无法证明纹状体内的基因型特异性衰老效应。这项纵向研究的结果有些令人惊讶，因为它证明了TgHD与Wt动物的显著差异老化模式。尽管似乎TgHD大鼠模型在12月龄时还没有充分的疾病表达，但由于对亨廷顿病的早期疾病机制仍有不完全的理解，因此进一步验证该模型是非常有益的。(C)2011 Elsevier Inc. All rights reserved.
We aimed to characterize the transgenic Huntington rat model with in vivo imaging and identify sensitive and reliable biomarkers associated with early and progressive disease status. In order to do so, we performed a multimodality (DTI and PET) longitudinal imaging study, during which the same TgHD and wildtype (Wt) rats were repetitively scanned. Surprisingly, the relative ventricle volume was smaller but increased faster in TgHD compared to Wt animals. DTI (mean, axial, radial diffusivity) revealed subtle genotype-specific aging effects in the striatum and its surrounding white matter, already in the presymptomatic stage. Using F-18-FDG and F-18-Fallypride PET imaging, we were not able to demonstrate genotype-specific aging effects within the striatum. The outcome of this longitudinal study was somewhat surprising as it demonstrated a significant differential aging pattern in TgHD versus Wt animals. Although it seems that the TgHD rat model does not have a sufficient expression of disease yet at the age of 12 months, further validation of this model is highly beneficial since there is still an incomplete understanding of the early disease mechanisms of Huntington's disease. (C) 2011 Elsevier Inc. All rights reserved.