Temporal effects of thyroid hormone (TH) and decabrominated diphenyl ether (BDE209) on Purkinje cell dendrite...

Thyroid hormones (TH) 3,3',4-tri-iodothyronine (T3) and 3,3',4,4'-tetra-iodothyronine (T4) plays crucial role in cerebellar development. Deficiency of TH consistently results in aberrant growth and development of the cerebellum including reduced growth and branching of the Purkinje cells. In rodents, the critical period of thyroid hormone action on cerebellum development is within the first two to three weeks, after which thyroid hormone replacement cannot fully reverse abnormal cerebellar development induced by thyroid hormone insult. Decabrominated diphenyl ether (BDE209) is an industrial reagent used as an additive flame retardant to reduce flammability of various commercial and household produce. BDE209 has bio-accumulative potential and is neurotoxic. Previously, we have shown that T4 (10-8 M) induced extensive dendrite arborization of Purkinje cells and low dose BDE209 (10-10 M) remarkably suppressed TH-induced Purkinje cell dendrite arborization. In the present study, we show that the critical period for TH-induced Purkinje cell growth and dendrite arborization in culture is much earlier than reported in animal models. Also, we show for the first time that low dose BDE209 suppressed TH-induced dendrite arborization in a time-dependent manner. Taken together, our study indicates that hypothyroidism and exposure to BDE209 during critical stage of cerebellar development can lead to impaired Purkinje cell growth and dendrite arborization and may consequently disrupt normal cerebellar functions.