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Developmental Exposure to A Commercial PBDE Mixture: Effects on Protein Networks in the Cerebellum and Hippocampus of Rats
Citation:
Kodavanti, P., J. Royland, C. Osorio, W. Winnik, P. Ortiz, L. Lei, R. Ramabhadran, AND O. Alzate. Developmental Exposure to A Commercial PBDE Mixture: Effects on Protein Networks in the Cerebellum and Hippocampus of Rats. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 123(5):428-436, (2015).
Impact/Purpose:
Title was modified for publication from: "Developmental Exposure to DE-71, A Commercial PBDE Mixture Alters Protein Network Associated with Energy Metabolism, Oxidative Stress, Plasticity, and Growth of the Nervous System in Rat Cerebellum and Hippocampus" Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants in domestic and industrial applications including computers, television sets, and mobile phones; also in furniture, textiles, insulation boards, mattresses, and upholstery furnishings (Alaee et al. 2003). Like polychlorinated biphenyls (PCBs), PBDEs are structurally similar synthetic chemicals comprised of two phenyl rings linked by oxygen (thus the designation as "ethers"; Figure 1). They are ubiquitous in the environment, where they bioaccumulate, becoming toxic to animals and humans (Guo et al. 2011; Kodavanti et al. 2008; Shaw et al. 2010). Levels of PBDEs have been reported to be increasing in some parts of the environment, in human blood, and milk (McDonald 2005; Petreas et al. 2003).
Description:
BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are structurally similar topolychlorinated biphenyls (PCBs) and have both central (learning and memory deficits) and peripheral (motor dysfunction) neurotoxic effects at concentrations/doses similar to those of PCBs. The cellular and molecular mechanisms for these neurotoxic effects are not fully understood; however, several studies have shown that PBDEs affect thyroid hormones, cause oxidative stress, and disrupt Ca2+ -mediated signal transduction. Changes in these signal transduction pathways can lead to differential gene regulation with subsequent changes in protein expression, which can affect the development and function of the nervous system.OBJECTIVE: In this study, we examined the protein expression profiles in the rat cerebellum and hippocampus following developmental exposure to a commercial PBDE mixture, DE-71. METHODS: Pregnant rats (Long Evans) were dosed perinatally with 0 or 30.6 mg/kg/day of DE-71 from gestation day 6 through sampling on postnatal day (PND) 14. Proteins from the cerebellum and hippocampus were extracted, expression differences were detected by two dimensional difference gel electrophoresis (2D DIGE), and proteins were identified by tandem mass spectrometry (MS/MS). Protein network interaction analysis was performed with Ingenuity® Pathway Analysis and proteins of interest were validated via Western blotting. RESULTS: Four proteins were found to be significantly differentially-expressed in the cerebellumfollowing DE-71 exposure while 70 proteins were significantly differentially-expressed in the hippocampus. The differentially-expressed proteins had roles in mitochondrial energy metabolism, oxidative stress, apoptosis, calcium signaling, and growth of the nervous system. CONCLUSIONS: Results suggest that changes in energy metabolism and processes related to neuro-plasticity and growth may be involved in the developmental neurotoxicity of PBDEs.
