Proceedings of The Physiological Society

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, PC235

Poster Communications

Effect of Hexabromocyclododecane on TH-mediated action in the developing brain

K. Ibhazehiebo1,2, T. Iwasaki1, N. Shimokawa1, N. Koibuchi1

1. Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi, Japan. 2. Physiology, University of Benin, Benin, Edo, Nigeria.

Thyroid hormones (THs) are critical for normal cerebellar development and function. Hypothyroidism has consistently resulted in abnormal growth, development, and function of the cerebellum including reduced growth, branching of the Purkinje cell dendrites, and exten sion of granule cell neurites. Hexabromocyclododecane (HBCD) is a brominated flame retardant used in a variety of household and commercial products including thermoplastic polymers and textile. It is currently a global environmental contaminant with detectable levels in both biotic and abiotic samples. Recent studies have shown that perinatal exposure to HBCD may alter spontaneous motor activity, disrupt learning and memory. Previously, we have shown that T4 (10 nM) treatment led to extensive dendrite arborization by Purkinje cells and low dose HBCD (10 pM) remarkably suppressed TH-induced Purkinje cell dendrite arborisation. In the present study, using primary cerebellar culture derived from new born rats, we show that time of withdrawal of T4 treatment is essential in Purkinje cell dendritogenesis. New born Wistar rats were decapitated under diethyl ether anesthesia on post natal day 1. The cerebella were digested with papain and dissociated cells were suspended in a serum-free medium without TH and plated in wells of chamber slides at a density of 2.5x105 cells /0.2 ml. The slides were pre-coated with 0.1 mg/ml poly-L-lysine. Next day after cell plating, the culture was treated with T4, and then subsequently withdrawn in a time-dependent manner. Half of the culture medium was replaced with fresh medium every 2-3 days for 17 days. Also, we show that HBCD suppresses TH-mediated Purkinje cell dendrite arborization in a time-dependant manner in vitro. Furthermore, we also showed that low dose HBCD significantly impaired TH-mediated granule cell neurite extension in vitro in Wistar rats. Taken together, our study shows that exposure to low dose HBCD can lead to impaired TH-mediated morphogenetic events in the developing Cerebellum and may consequently disrupt normal brain development and functions.

Where applicable, experiments conform with Society ethical requirements