Neuroanatomic and behavioral traits for autistic disorders in age-specific restricted index selection mice.
Neuroanatomic and behavioral traits for autistic disorders in age-specific restricted index selection mice.
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DOI：
10.1016/j.neuroscience.2011.05.017
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发表时间：
2011-08-25
期刊：
影响因子：
3.3
通讯作者：
Dong, H.
中科院分区：
文献类型：
--
作者：
Meng, L.;Lu, L.;Murphy, K. M.;Yuede, C. M.;Cheverud, J. M.;Csernansky, J. G.;Dong, H.
神经发育障碍如自闭症的发病机制被认为受到遗传和环境因素之间相互作用的影响，需要适当的动物模型来评估这些因素对相关神经发育表型的影响。通过年龄特异性限制性指数选择从获自哈兰Sprague-Dawley（; Indianapolis，IN）的基线随机繁殖ICR小鼠群体产生一组近交系小鼠品系（Atchley品系），包括A12（E+L0）和A22（E-L0）。与A22品系相比，A12小鼠早期（P0-P10）体重增量显著增加，晚期（P28-P56）体重增量变化极小。我们发现，这些菌株在脑重量、脑体积、细胞增殖和某些脑区域的FGF-2水平方面也存在差异。具体而言，在P10和P28时，A12小鼠的脑重量和体积显著大于A22小鼠。溴脱氧尿苷（BrdU）标记的增殖细胞的定量分析表明，在A12株的BrdU阳性细胞的数量显着更多的额叶皮质和较少的齿状回比在A22株在P28。Western blot显示，成纤维细胞生长因子-2（FGF-2），而不是脑源性神经营养因子（BDNF），表达显着增加，在A12品系在P28的额叶皮质。此外，A12小鼠在P28时表现出减少的品系内社会互动和增加的重复刻板行为。我们的研究表明，A12小鼠可能部分模仿神经发育障碍（如自闭症谱系障碍）患者的解剖和行为特征，因此可能会深入了解其发病机制中涉及的发育机制。
The pathogenesis of neurodevelopmental disorders such as autism is believed to be influenced by interactions between genetic and environmental factors, and appropriate animal models are needed to assess the influence of such factors on relevant neurodevelopmental phenotypes. A set of inbred mouse strains (Atchley strains) including A12 (E+L0) and A22 (E-L0) were generated by age-specific restricted index selection from a baseline random-bred ICR mouse population obtained from Harlan Sprague-Dawley (; Indianapolis, IN). As compared with the A22 strain, A12 mice had significantly increased early (P0-P10) body weight gain with minimal changes in late (P28 to P56) body weight gain. We found that these strains also differed in brain weight, brain volume, cell proliferation, and FGF-2 levels in certain brain regions. Specifically, brain weight and volume were significantly greater in A12 mice than that in A22 mice at P10 and P28. Quantitative analysis of Bromodeoxyuridine (BrdU) labeling of proliferating cells showed that the number of BrdU-positive cells in the A12 strain was significantly greater in the frontal cortex and lesser in the dentate gyrus than that in the A22 strain at P28. Western blot revealed that fibroblast growth factors-2 (FGF-2), but not brain-derived neurotrophic factor (BDNF), expression was significantly increased in the frontal cortex of A12 strain at P28. Also, A12 mice exhibited decreased intra-strain social interaction and increased repetitive stereotyped behaviors at P28. Our study suggests that A12 mice may partially mimic the anatomic and behavioral traits of patients with neurodevelopmental disorders such as autism spectrum disorders, and therefore may yield insights into the developmental mechanisms involved in their pathogenesis.
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DOI：
10.1523/jneurosci.1161-10.2010
发表时间：
2010-11-03
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Giza J;Urbanski MJ;Prestori F;Bandyopadhyay B;Yam A;Friedrich V;Kelley K;D'Angelo E;Goldfarb M
通讯作者：
Goldfarb M
DOI：
10.1016/j.ijdevneu.2010.02.003
发表时间：
2010-05-01
影响因子：
1.8
作者：
Kim, Jinsook;Gale, Karen;Kondratyev, Alexei
通讯作者：
Kondratyev, Alexei
影响因子：
2.9
作者：
Cheh, Michelle A.;Millonig, James H.;Wagner, George C.
通讯作者：
Wagner, George C.
影响因子：
5.7
作者：
Carper, RA;Moses, P;Courchesne, E
通讯作者：
Courchesne, E
影响因子：
10.6
作者：
Carper, RA;Courchesne, E
通讯作者：
Courchesne, E