Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism.
Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism.
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DOI：
10.1016/j.brainres.2012.03.041
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发表时间：
2012-05-21
期刊：
影响因子：
2.9
通讯作者：
Poptani H
中科院分区：
文献类型：
--
作者：
Kumar M;Kim S;Pickup S;Chen R;Fairless AH;Ittyerah R;Abel T;Brodkin ES;Poptani H
弥散张量成像 (DTI) 在检测自闭症谱系障碍 (ASD) 的大脑结构和连接表型方面高度敏感。由于 ASD 的核心症状之一是社交能力下降（寻求社交互动的倾向减少），我们假设 DTI 在检测与小鼠模型中社交能力下降相关的神经表型方面会很敏感。相对于 C57BL/6J (B6) 小鼠，幼年 BALB/cJ 小鼠表现出社交能力下降。我们对 BALB/cJ (n=32) 和 B6 (n=15) 小鼠在出生后 30、50 和 70 天时在三腔装置中进行社交方法测试和体内纵向 DTI，以评估 DTI 和社交能力之间的相关性，并评估这两种品系之间 DTI 参数的差异。根据白质（胼胝体、内囊和外囊）和灰质（大脑皮层、额叶运动皮层、海马、丘脑和杏仁核）区域与 ASD 的相关性，对体内 DTI 数据的分数各向异性 (FA) 和平均扩散率 (MD) 值进行分析。 30 日龄的 BALB/cJ 小鼠中，海马和额叶运动皮层的社交能力与 FA 之间存在中度但显着的负相关（p<0.05）。在所有三个时间点，在大多数白质和灰质区域观察到 BALB/cJ 和 B6 小鼠之间 FA 和 MD 值的显着差异。 BALB/cJ 和 B6 之间还观察到丘脑和额叶运动皮层 FA 和 MD 值发育轨迹的显着差异，表明 BALB/cJ 小鼠的连接性相对不足。这些结果表明，DTI 可作为一种体内、非侵入性成像方法来评估神经发育和行为障碍小鼠模型中大脑连接的发育轨迹。
Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70 days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30 days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders.
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