2007 Fiscal Year Final Research Report Summary
An in vitro screening system for assessment of environmental chemicals on brain
| Project/Area Number |
17510059
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
KURODA Junko (木村 純子) Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist (20142151)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Isao Tokyo Metropolitan Organization for Medical Research, Staff Scientist (30124415)
KURODA Yoichiro Tokyo Metropolitan Organization for Medical Research, Staff Scientist (30073084)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Environment / Brain, nervous system / Development, differentiation / Environmental chemicals / PCB / Neurotoxicity |
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| Research Abstract |
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
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