Postnatal low-concentration arsenic exposure induces autism-like behavior and affects frontal cortex neurogenesis in rats
Postnatal low-concentration arsenic exposure induces autism-like behavior and affects frontal cortex neurogenesis in rats
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出生后低浓度砷暴露诱发大鼠自闭症样行为并影响额叶皮层神经发生
DOI：
10.1016/j.etap.2018.07.012
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
赵魏情
中科院分区：
文献类型：
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作者：
崔玉霞;周浩;赵魏情
本研究旨在探讨出生后低浓度砷暴露对大鼠学习能力、社会技能和额叶皮质神经发生的影响。于生后4-10天（P4-P10）建立饮水砷染毒大鼠模型。实验动物分为对照组、15 μg/L As 2 O3水组、30 μg/L As 2 O3水组和45 μg/L As 2 O3水组。认知功能采用Morris水迷宫测试，焦虑样行为采用旷场测试和明暗箱测试，社交技能采用社交互动测试。在砷暴露后的不同时间点，对每个实验组的幼鼠额叶皮质进行切片。采用苏木精-伊红染色、尼氏染色和双皮质素（DCX）免疫组化染色观察额叶皮质神经元的形态和神经发生。砷浓度与学习和社会技能缺陷呈显著正相关，与对照组相比，砷暴露组焦虑样行为显著增加（均P <0. 05）。砷暴露急性期外颗粒层和外锥体层的异常形态变化与水砷浓度呈正相关。然而，在砷暴露后五周，额叶皮质形态恢复。此外，免疫组织化学显示，与对照组相比，暴露于砷的组在外部颗粒层和外部锥体层中表现出显著更高水平的DCX表达（所有Ps < 0.001）。30 μg/L和45 μg/L砷暴露组在暴露后5周仍有部分DCX表达。总之，出生后低浓度砷暴露损害学习和社会技能，增加焦虑样行为，异常的额叶皮层神经发生可能是这些影响的机制。
This study aimed to explore the effects of postnatal low-concentration arsenic exposure on learning, social skillsand frontal cortex neurogenesis in rats. Water-based arsenic exposure rat models were established on postnataldays 4–10 (P4-P10). The experimental animals were divided into four groups: the control group, a 15 μg/L As2O3 water group, a 30 μg/L As2O3 water group, and a 45 μg/L As2O3 water group. Cognitive function was examined with the Morris water maze, anxiety-like behavior with the open field test and light-dark box test, and social skills with a social interaction test. The frontal cortices of pups from each experimental group were sectioned at various time points after arsenic exposure. The morphologies and neurogenesis of the neurons in the frontal cortices were observed by hematoxylin-eosin staining, Nissl staining, and doublecortin (DCX) immunostaining. Significant positive correlations between arsenic concentration and deficits in learning and social skills were found, and the arsenic exposure groups showed significant increases in anxiety-like behavior compared with the control group (all Ps < 0.05). Abnormal morphologic changes in the external granular layer and external pyramidal layer were positively correlated with the water arsenic concentration in the acute phase of arsenic exposure. However, at five weeks after arsenic exposure, the frontal cortex morphology was restored. Moreover, immunohistochemistry revealed that compared to the control group, the groups that were exposed to arsenic exhibited significantly higher levels of DCX expression in the external granular and external pyramidal layers (all Ps < 0.001). Furthermore, the 30 μg/L and 45 μg/L arsenic exposure groups still showed some DCX expression at five weeks after exposure. In conclusion, postnatal low-concentration arsenic exposure impaired learning and social skills and increased anxiety-like behaviors, and abnormal frontal cortex neurogenesis may be the mechanism underlying these effects.