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产前暴露于双酚 A 的新生小鼠表现出多动和皮质发育缺陷。

Newborn mice exposed prenatally to bisphenol A show hyperactivity and defective neocortical development.

机构信息

Department of Anatomy, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.

Department of Life Science, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan.

出版信息

Toxicology. 2014 Sep 2;323:51-60. doi: 10.1016/j.tox.2014.06.009. Epub 2014 Jun 20.

Abstract

The central nervous system is especially susceptible to toxic insults during development. Prenatal administration of bisphenol A (BPA) induces histologic anomalies in the dorsal telencephalon of the embryo. Whether these anomalies affect the morphogenesis and maturation of neuronal function of the newborn neocortex, however, is unknown. To evaluate the neurodevelopmental and behavioral effects of prenatal BPA exposure at 20 and 200μg/kg/day in newborn mice, we performed a detailed histologic analysis of the neocortex and tested for the presence of behavioral abnormalities in newborn mice prenatally exposed to BPA using our newly developed behavioral test. Observations of newborn mice prenatally exposed to BPA revealed abnormal neuronal distribution and layer formation, hypoplasia of layer 6b, and abnormal dopaminergic neuronal projections in the neocortex. Further, the newborn mice exhibited hyperactivity. These findings suggest that prenatal BPA exposure induces neurobehavioral toxicity associated with abnormal dopaminergic neuronal projections, and abnormal corticogenesis and lamination. Histologic and behavioral analyses of newborn mice are considered useful for assessing the neurodevelopmental and behavioral toxicity of chemicals.

摘要

中枢神经系统在发育过程中尤其容易受到有毒物质的侵害。产前给予双酚 A(BPA)会导致胚胎背侧端脑出现组织学异常。然而,这些异常是否会影响新生儿新皮质的神经元功能的形态发生和成熟尚不清楚。为了评估新生小鼠在 20 和 200μg/kg/天时暴露于 BPA 的神经发育和行为影响,我们对新皮质进行了详细的组织学分析,并使用我们新开发的行为测试来检测新生小鼠在产前暴露于 BPA 时是否存在行为异常。对产前暴露于 BPA 的新生小鼠的观察显示,神经元分布和层形成异常,6b 层发育不良,以及新皮质中多巴胺能神经元投射异常。此外,新生小鼠表现出过度活跃。这些发现表明,产前 BPA 暴露会引起与异常多巴胺能神经元投射、异常皮质发生和分层相关的神经行为毒性。对新生小鼠的组织学和行为分析被认为可用于评估化学物质的神经发育和行为毒性。

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