Prenatal exposure to bisphenol A impacts neuronal morphology in the hippocampal CA1 region in developing and aged mice.
Prenatal exposure to bisphenol A impacts neuronal morphology in the hippocampal CA1 region in developing and aged mice.
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DOI：
10.1007/s00204-015-1485-x
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发表时间：
2016-03
影响因子：
6.1
通讯作者：
Tohyama C
中科院分区：
文献类型：
--
作者：
Kimura E;Matsuyoshi C;Miyazaki W;Benner S;Hosokawa M;Yokoyama K;Kakeyama M;Tohyama C
双酚A （BPA）是一种广泛用于聚碳酸酯塑料和环氧树脂的原料成分，据报道，暴露于低剂量BPA的母鼠所生的后代会产生发育性神经毒性；然而，其毒性机制尚不清楚。为了研究子宫内BPA暴露对神经元形态的影响，我们研究了产前暴露于低剂量BPA的老年小鼠和发育中小鼠海马CA1的脊柱密度和树突生长。在妊娠第8.5 ~ 17.5/18.5天，以0、40或400 μg/kg体重/天的低剂量给药妊娠小鼠。小鼠后代在3周或14个月时被安乐死，并分析其大脑中表达gfp的神经元的树突状树突或海马CA1高尔基染色神经元的脊柱密度。无论剂量如何，子宫内BPA暴露降低了14个月大小鼠海马CA1的脊柱密度。BPA暴露剂量为400 μg/kg体重/d的3周龄大鼠脑发育过程中，基底树突的总长度和分枝数均有所减少，但顶端树突的分枝数未见减少。在子宫内，低剂量的BPA暴露会在发育过程中破坏海马CA1神经元的形态，并且这种破坏被认为会持续到成年。本文的在线版本（doi:10.1007/s00204-015-1485-x）包含补充材料，仅供授权用户使用。
Bisphenol A (BPA), a widely used raw component of polycarbonate plastics and epoxy resins, has been reported to induce developmental neurotoxicity in offspring born to dams exposed to low doses of BPA; however, the toxicity mechanism remains elusive. To study the effects of in utero BPA exposure on neuronal morphology, we studied spine density and dendritic growth in the hippocampal CA1 of aged mice and developing mice prenatally exposed to low doses of BPA. Pregnant mice were orally administered BPA at a low dose of 0, 40, or 400 μg/kg body weight/day on gestational days 8.5–17.5/18.5. Mouse progenies were euthanized at 3 weeks or 14 months, and their brains were analyzed for dendritic arborization of GFP-expressing neurons or spine densities of Golgi-stained neurons in the hippocampal CA1. Regardless of the dose, in utero BPA exposure reduced spine densities in the hippocampal CA1 of the 14-month-old mice. In the developing brain from the 3-week-old mice born to dams exposed to BPA at a dose of 400 μg/kg body weight/day, overall length and branching number of basal dendrites but not apical dendrites were decreased. In utero low doses of BPA exposure disrupts hippocampal CA1 neuronal morphology during development, and this disruption is believed to persist in adulthood. The online version of this article (doi:10.1007/s00204-015-1485-x) contains supplementary material, which is available to authorized users.