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致病因素，如多动症和/或自闭症，这些疾病现在正在成为美国和日本的一个主要社会问题。对动物和儿童的研究表明，正常发生的化学物质（如铅）浓度的细微变化，以及有毒物质（如铅）的存在，汞或多氯联苯-可以产生深远的和永久的变化，在发展中的神经系统。这些变化可能导致智力下降和生殖系统的改变。OECD和EHP已经提出了用啮齿动物实验来测试化学品的发育神经毒性的指南，这需要大量的成本和时间以及动物。有必要建立一种方便、灵敏、简单的化学物质发育神经毒性筛查系统。我们开发了两种发育神经毒性的定量测定系统， ...更多信息 啮齿动物原代脑培养。小脑神经元树突发育的体外筛选系统。这提供了一个方便的，可重复的，灵敏的测定，以测试化学品对甲状腺激素依赖的神经发育的影响。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。我们指出，即使在低剂量下，一些羟基PCB也会抑制浦肯野细胞树突的甲状腺激素依赖性发育（Kimura黑田等人，等人：Dev. Brain Res 154：259，2005）。利用小脑或大脑神经元突触形成测量的体外筛选系统。这提供了一个方便的，可重复的，灵敏的检测化学品对生理活性物质，包括激素和神经活动依赖性物质，这是重要的正常大脑发育的影响，我们希望改进这些检测方法，并提出他们的第一个筛选系统发育神经毒性。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