Prenatal exposure to bisphenol A impacts midbrain dopamine neurons and hippocampal spine synapses in non-human primates.
Prenatal exposure to bisphenol A impacts midbrain dopamine neurons and hippocampal spine synapses in non-human primates.
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DOI：
10.1016/j.neuro.2013.01.001
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发表时间：
2013-03
期刊：
影响因子：
3.4
通讯作者：
Leranth, Csaba
中科院分区：
文献类型：
--
作者：
Elsworth, John D.;Jentsch, J. David;VandeVoort, Catherine A.;Roth, Robert H.;Redmond, D. Eugene, Jr.;Leranth, Csaba
双酚 A (BPA) 在树脂、塑料和纸制品制造中的广泛使用导致大多数人经常接触这种内分泌干扰物。一些啮齿动物研究表明，BPA 会对大脑发育产生有害影响。然而，由于不能依靠啮齿动物模型来预测人类在发育过程中接触 BPA 的后果，因此研究 BPA 对非人类灵长类动物大脑发育的影响非常重要。先前的研究表明，BPA 优先针对腹侧中脑的多巴胺神经元和海马的谷氨酸能神经元，因此本研究在非人类灵长类动物的胎儿和幼年发育阶段检查了这些系统对低剂量 BPA 暴露的敏感性。怀孕的恒河猴在妊娠最后 2 个月接触相对较低水平的 BPA，会导致胎儿腹侧中脑和海马体出现异常。具体来说，光学显微镜显示暴露于 BPA 的胎儿中脑中表达酪氨酸羟化酶（多巴胺）的神经元减少，电子显微镜发现海马 CA1 区域的棘突触减少。相比之下，给幼年长尾猴（14-18 个月大）注射 BPA 对这些指数、纹状体和前额皮质中的多巴胺和血清素浓度、或测试工作记忆能力的认知任务的表现没有影响。这些数据表明，BPA 对灵长类动物的大脑发育产生年龄依赖性的有害影响，其血液浓度在仅与 BPA 环境接触的人类所测量的范围内。
Prevalent use of bisphenol-A (BPA) in the manufacture of resins, plastics and paper products has led to frequent exposure of most people to this endocrine disruptor. Some rodent studies have suggested that BPA can exert detrimental effects on brain development. However as rodent models cannot be relied on to predict consequences of human exposure to BPA during development, it is important to investigate the effects of BPA on non-human primate brain development. Previous research suggests that BPA preferentially targets dopamine neurons in ventral mesencephalon and glutamatergic neurons in hippocampus, so the present work examined the susceptibility of these systems to low dose BPA exposure at the fetal and juvenile stages of development in non-human primates. Exposure of pregnant rhesus monkeys to relatively low levels of BPA during the final 2 months of gestation, induced abnormalities in fetal ventral mesencephalon and hippocampus. Specifically, light microscopy revealed a decrease in tyrosine hydroxylase-expressing (dopamine) neurons in the midbrain of BPA-exposed fetuses and electron microscopy identified a reduction in spine synapses in the CA1 region of hippocampus. In contrast, administration of BPA to juvenile vervet monkeys (14–18 months of age) was without effect on these indices, or on dopamine and serotonin concentrations in striatum and prefrontal cortex, or on performance of a cognitive task that tests working memory capacity. These data indicate that BPA exerts an age-dependent detrimental impact on primate brain development, at blood levels within the range measured in humans having only environmental contact with BPA.
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