Shah Disha, Deleye Steven, Verhoye Marleen, Staelens Steven, Van der Linden Annemie
Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp Belgium.
Molecular Imaging Center Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp Belgium.
Neuroimage. 2016 Jan 15;125:571-577. doi: 10.1016/j.neuroimage.2015.10.073. Epub 2015 Oct 28.
The existence of numerous interesting mouse models of neurological disorders enables the investigation of causal relations between pathological events and the effect of treatment regimes. However, mouse models of a specific neurological disease are often generated using different background strains, which raises the question whether the observed effects are specific to pathology or depend on the used strain. This study used two independent in vivo functional imaging techniques to evaluate whether mouse strain differences exist in functional connectivity (FC) and brain glucose metabolism i.e. indirect measures of neuronal activity. For this purpose, C57BL/6, BALB/C and SJL mice (N=15/group, male) were evaluated using resting-state functional MRI (rsfMRI) and static [18F]-fluorodeoxyglucose Positron Emission Tomography ([18F]-FDG PET). RsfMRI and [18F]-FDG PET data were analyzed with independent component analysis (ICA). FC was quantified by calculating the mean network-specific FC strength and [18F]-FDG uptake was quantified by calculating the mean network-specific standard uptake value corrected for plasma glucose levels and body weight (SUVglu). The ICA results showed spatially similar neurological components in the rsfMRI and [18F]-FDG PET data, suggesting that patterns of metabolic covariance in the mouse brain reflect FC networks. Comparing FC and [18F]-FDG data showed that strain-dependent differences in brain activity exist for several brain networks i.e. the frontal, cingulate, (hypo)thalamus, striatum, and sensorimotor networks. The results of this study have implications for the interpretation of in vivo functional imaging data in mouse models of neurological disorders generated on different background strains.
众多有趣的神经疾病小鼠模型的存在，使得人们能够研究病理事件与治疗方案效果之间的因果关系。然而，特定神经疾病的小鼠模型通常是使用不同的背景品系构建的，这就引发了一个问题，即观察到的效果是特定于病理学的，还是取决于所使用的品系。本研究使用了两种独立的体内功能成像技术，来评估在功能连接性（FC）和脑葡萄糖代谢（即神经元活动的间接指标）方面是否存在小鼠品系差异。为此，使用静息态功能磁共振成像（rsfMRI）和静态[18F] - 氟脱氧葡萄糖正电子发射断层扫描（[18F] - FDG PET）对C57BL / 6、BALB / C和SJL小鼠（每组N = 15只，雄性）进行评估。rsfMRI和[18F] - FDG PET数据采用独立成分分析（ICA）进行分析。通过计算平均网络特异性FC强度来量化FC，通过计算经血浆葡萄糖水平和体重校正后的平均网络特异性标准摄取值（SUVglu）来量化[18F] - FDG摄取。ICA结果显示，rsfMRI和[18F] - FDG PET数据在空间上具有相似的神经成分，这表明小鼠大脑中的代谢协方差模式反映了FC网络。比较FC和[18F] - FDG数据表明，几个脑网络（即额叶、扣带回、（下）丘脑、纹状体和感觉运动网络）存在脑活动的品系依赖性差异。本研究结果对解释在不同背景品系上构建的神经疾病小鼠模型中的体内功能成像数据具有重要意义。
