An in vitro method to study the effects of thyroid hormone-disrupting chemicals on neuronal development.

Thyroid hormones (THs) play critical roles for normal cerebellar development. It has been reported that several environmental chemicals may affect cerebellar development through TH system. One such example is the suppression of TH receptor (TR)-mediated transcription by polybrominated diphenyl ethers (PBDEs). To determine the effect of these chemicals on brain development, we established a primary culture system of rat cerebellar Purkinje cells. Using this system, as low as 10(-10)M TH induced Purkinje cell dendritic arborization and such effect was dose-dependent. We examined the effect of decabromodiphenyl ether (BDE209) using this system. Dendritic development of the Purkinje cells was suppressed by 10(-10)M BDE209, that was compatible to the result of the suppression of TR-mediated transcription by using reporter gene assay. These results suggest that TH plays a pivotal role in the development of the Purkinje cell dendrites. Together with in vitro assay system such as reporter gene assay and liquid chemiluminescent DNA-pull down assay, an in vitro protein-DNA binding assay, these assay systems provide us with precise information about environmental chemicals on brain development.