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
