Petrella L I, Cai Y, Sereno J V, Gonçalves S I, Silva A J, Castelo-Branco M
Institute of Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal.
Center for Neuroscience and Cell Biology - Institute of Biomedical Imaging and Life Science (CNC.IBILI), University of Coimbra, Coimbra, Portugal.
Genes Brain Behav. 2016 Sep;15(7):637-46. doi: 10.1111/gbb.12305. Epub 2016 Jul 5.
Neurofibromatosis type-1 (NF1) is a common neurogenetic disorder and an important cause of intellectual disability. Brain-behaviour associations can be examined in vivo using morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to study brain structure. Here, we studied structural and behavioural phenotypes in heterozygous Nf1 mice (Nf1(+/-) ) using T2-weighted imaging MRI and DTI, with a focus on social recognition deficits. We found that Nf1(+/-) mice have larger volumes than wild-type (WT) mice in regions of interest involved in social cognition, the prefrontal cortex (PFC) and the caudate-putamen (CPu). Higher diffusivity was found across a distributed network of cortical and subcortical brain regions, within and beyond these regions. Significant differences were observed for the social recognition test. Most importantly, significant structure-function correlations were identified concerning social recognition performance and PFC volumes in Nf1(+/-) mice. Analyses of spatial learning corroborated the previously known deficits in the mutant mice, as corroborated by platform crossings, training quadrant time and average proximity measures. Moreover, linear discriminant analysis of spatial performance identified 2 separate sub-groups in Nf1(+/-) mice. A significant correlation between quadrant time and CPu volumes was found specifically for the sub-group of Nf1(+/-) mice with lower spatial learning performance, suggesting additional evidence for reorganization of this region. We found strong evidence that social and spatial cognition deficits can be associated with PFC/CPu structural changes and reorganization in NF1.
1型神经纤维瘤病（NF1）是一种常见的神经遗传性疾病，也是智力残疾的重要原因。可以使用形态计量磁共振成像（MRI）和扩散张量成像（DTI）在体内检查脑-行为关联，以研究脑结构。在此，我们使用T2加权成像MRI和DTI研究了杂合Nf1小鼠（Nf1(+/-)）的结构和行为表型，重点关注社会认知缺陷。我们发现，在参与社会认知的感兴趣区域，即前额叶皮层（PFC）和尾状核-壳核（CPu），Nf1(+/-)小鼠的体积比野生型（WT）小鼠大。在这些区域内外的皮质和皮质下脑区的分布式网络中发现了更高的扩散率。在社会认知测试中观察到显著差异。最重要的是，在Nf1(+/-)小鼠中，发现了社会认知表现与PFC体积之间存在显著的结构-功能相关性。空间学习分析证实了突变小鼠中先前已知的缺陷，平台穿越、训练象限时间和平均接近度测量结果也证实了这一点。此外，对空间表现的线性判别分析在Nf1(+/-)小鼠中识别出2个独立的亚组。专门针对空间学习表现较低的Nf1(+/-)小鼠亚组，发现象限时间与CPu体积之间存在显著相关性，这为该区域的重组提供了额外证据。我们发现有力证据表明，社会和空间认知缺陷可能与NF1中的PFC/CPu结构变化和重组有关。
