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

用于评估大脑环境化学物质的体外筛选系统

• 批准号: 17510059
• 负责人: KURODA Junko
• 金额: $ 2.43万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17510059/
• 关键词: Environment; Brain, nervous system; Development, differentiation; Environmental chemicals; PCB; Neurotoxicity; 脳・神経

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

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，例如注意力缺陷多动症和/或自闭症，这些疾病现已成为美国和日本的一个主要社会问题。现在，通过对动物和儿童的研究清楚地表明，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。这些变化可能导致精神表现下降和生殖系统改变。 OECD 和 EHP 提出了使用啮齿类动物实验来测试化学物质的发育神经毒性的指南，这需要巨大的成本、时间和动物。有必要建立方便、灵敏、简便的化学品发育神经毒性筛查系统。我们使用啮齿动物原代脑培养物开发了两种用于发育神经毒性的定量测定系统。1)。使用测量小脑神经元树突发育的体外筛选系统。这提供了一种方便、可重复、灵敏的测定法来测试化学物质对甲状腺激素依赖性神经发育的影响。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。我们表明，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 Kuroda等人：Dev. Brain Res 154：259，2005）2）。使用测量小脑或大脑神经元突触形成的体外筛选系统。这提供了一种方便、可重复、灵敏的测定方法来测试化学物质对生理活性物质（包括激素和神经活动依赖性物质）的影响，这些物质对正常大脑发育很重要。我们希望改进这些测定方法，并建议将它们用于发育神经毒性的首次筛选系统。较少的

项目成果

自閉症の原因・発症過程と分子神経生物学-一因としての環境化学物質汚染-

自闭症的病因、发病过程和分子神经生物学 - 环境化学污染是一个促成因素 -

• 发表时间: 2006
• 期刊: 医学のあゆみ 217
• 作者: Kimura-Kuroda J;Nagata I;Kuroda Y.;Kuroda Y.;Junko Kimura-Kuroda;Junko Kimura-Kuroda;Isao Nagata;黒田洋一郎
• 通讯作者: 黒田洋一郎

Growth cone difference between CNS and PNS neurons in actin polymerization state and L1 expression, with special reference to their parallel and perpendicular orientation on aligned neurite bundles.

CNS 和 PNS 神经元在肌动蛋白聚合状态和 L1 表达方面的生长锥差异，特别是它们在对齐的神经突束上的平行和垂直方向。

• 发表时间: 2006
• 作者: Kimura-Kuroda J;Negishi T. Tashiro;T;Nagata I;T. Kuroda Y.;永田 功;Ngata I and Kimura-Kuroda J;Isao Naagata;Ngata I and Kimura-Kuroda J
• 通讯作者: Ngata I and Kimura-Kuroda J

Effects of OH-PCBs detected in human brains on developmental neurons. -In vitro screening of rodent neuronal cultures-

在人脑中检测到的 OH-PCB 对发育神经元的影响。

• 发表时间: 2005
• 作者: Kimura-Kuroda J;Nagata I;Negishi T;Kuroda Y.
• 通讯作者: Kuroda Y.

Attention-deficit and hyperactive neurobehavioural characteristics induced by perinatal hypothyroidism in rats

• DOI: 10.1016/j.bbr.2004.11.012
• 发表时间: 2005-04-30
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: Negishi, T;Kawasaki, K;Yoshikawa, Y
• 通讯作者: Yoshikawa, Y

Effects on developmental neurons of OH-PCBs detected in human brains. -2nd. Inhibitory effects on synapse formation in mouse cerebellar culture-

在人脑中检测到的 OH-PCB 对发育神经元的影响。

• 发表时间: 2006
• 作者: Kimura-Kuroda J;Negishi T. Tashiro;T;Nagata I;T. Kuroda Y.
• 通讯作者: T. Kuroda Y.