Molecular Targets of HBCDD in the Hippocampus Open Access

Aronoff, Elizabeth Barnett (2016)

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Over the years both environmental and health effects have been discovered surrounding the many halogenated organic compounds. Although the use of some compounds including polychlorinated biphenyls (PCBs) has been banned, many still remain in use including the brominated flame-retardant (BFRs) compounds. However, while polybrominated diphenyl ethers (PBDEs) have been discontinued, this has led to an increase in the use of hexabromocyclododecane (HBCDD) and other similar flame retardant compounds. While few studies have evaluated the neurotoxicity of HBCDD there have been many studies assessing the neurological effects of PBDE including the detrimental effects of exposure to PBDE on the hippocampus. The toxicity in the hippocampus has been associated with deficits in learning and memory and could also then result from exposure to HBCDD. Through both an in vitro and in vivo model this study will help to evaluate the neurotoxic effects of HBCDD in the hippocampus. We have demonstrated the general neurotoxicity using a neuroblastoma cell-line, SK-N-SH, by showing a significant increase in cell death following 24 h exposure to varying concentrations of HBCDD (0-25µM). Significant differences of levels of Ube3a expression were also found when exposing primary hippocampal cultures to HBCDD (0-2.5µM) for 8 days. A mouse model was used to demonstrate in vivo neurotoxicity of HBCDD (25mg/kg for 30 days). This showed a significant decrease in expression of hippocampal NMDAR 2B, Tau, CNPase, TH, and VMAT2 all crucial in multiple neurotransmitter systems. There was also a significant increase in Ube3a, mGluR2, GAP43, BDNF, PSA-NCAM, GAT1, and the D2 receptor in the hippocampus. This wide range of effects shows a significant disruption in the network of the hippocampus, which could lead to behavioral deficits including deficits in learning and memory comparable to those seen with similar compounds. These are the first data that begin to assess the toxicity of HBCDD in the hippocampus. The increasing exposure in the environment to HBCDD provides further support for future studies to continue evaluating its neurological effects.

Table of Contents

Introduction -- 1

Methods -- 7

Results -- 10

Discussion -- 13

Figures -- 21

References -- 29

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