An in vitro screening system for assessment of environmental chemicals on brain

包括内分泌干扰物在内的一些环境化学物质可能是各种大脑发育障碍的原因，如多动症和/或自闭症，这些在美国和日本正成为一个主要的社会问题。现在，从对动物和儿童的研究中可以清楚地看到，正常存在的化学物质(如激素)浓度的细微变化，以及铅、汞或多氯联苯等有毒物质的存在，可能会对发育中的神经系统产生深刻而永久的变化。这些变化可能会导致精神表现的下降和生殖系统的改变。OECD和EHP已经提出了使用啮齿动物实验来测试发育神经毒性的化学品的指导方针，这需要巨大的成本和时间和动物。因此，有必要建立一套简便、灵敏、简便的化学物质发育神经毒性筛选体系。我们使用…开发了两个发育神经毒性的定量检测系统更多的啮齿动物原代脑培养。测量小脑神经元树突发育的体外筛选系统。这为测试化学物质对甲状腺激素依赖神经发育的影响提供了一种方便、可重复性、灵敏的检测方法。众所周知，甲状腺激素对大脑发育很重要，甲状腺功能减退会导致克汀病和严重的神经障碍。我们发现一些羟基-多氯联苯甚至在低剂量下也能抑制浦肯野细胞树突状细胞的甲状腺激素依赖性发育(Kimura Kuroda，et.艾尔：Dev.大脑资源154：259,2005)2)。测量小脑或大脑神经元突触形成的体外筛选系统。这为测试化学物质对生理活性物质的影响提供了一种方便、可重复、灵敏的方法，包括激素和神经活动依赖物质，这些物质对正常的大脑发育是重要的。我们希望改进这些检测方法，并建议它们作为发育神经毒性的第一次筛查系统。较少

Some environmental chemicals including endocrine disrupters may be causal factors of various developmental disorders of the brain, such as ADHD and/or autism, which are now becoming a major social concern in the US and Japan.It is now clear from studies of animals and children that subtle changes in the concentrations of normally occurring chemicals such as hormones-as well as the presence of toxic agents like lead, mercury or PCBs-can produce profound and permanent changes in the developing nervous system. These changes can lead to decrements in mental performance and alterations of the reproductive system. OECD and EHP have propounded guidelines for the testing chemicals of developmental neurotoxicity using rodent animal experiments, which require huge cost and time and animals. It is necessary to establish a convenient, sensitive and simple screening system for developmental neurotoxicity of chemicals. We developed two quantitative assay systems for developmental neurotoxicity using … More rodent primary brain culture.1). In vitro screening system using measurement of dendritic development of cerebellar neurons. This provides a convenient, reproducible, sensitive assay to test effects of chemicals on thyroid-hormone-dependent neural development. Thyroid hormone is known to be important for brain development and hypothyroid causes cretinism with severe neural disorder. We indicated some hydroxy-PCB inhibited thyroid-hormone-dependent development of Purkinje cell dendrite even at low dose (Kimura Kuroda, et. al. : Dev. Brain Res 154 : 259, 2005).2). In vitro screening system using measurement of synapse formation of cerebellar or cerebral neurons. This provides a convenient, reproducible, sensitive assay to test effects of chemicals on physiologically active substances, including hormones and nervous activity-dependent-substances, which are important for normal brain development.We want to improve these assays and propose them for first screening system for developmental neurotoxicity. Less