Developmental exposure to a commercial PBDE mixture: Effects on protein networks in the cerebellum and hippocampus of rats

Abstract

Background: Polybrominated diphenyl ethers (PBDEs) are structurally similar to polychlorinatedbiphenyls (PCBs) and have both central (learning and memory deficits) and peripheral (motordysfunction) neurotoxic effects at concentrations/doses similar to those of PCBs. The cellular andmolecular mechanisms for these neurotoxic effects are not fully understood; however, several studieshave shown that PBDEs affect thyroid hormones, cause oxidative stress, and disrupt Ca 2+ -mediatedsignal transduction. Changes in these signal transduction pathways can lead to differential generegulation with subsequent changes in protein expression, which can affect the development andfunction 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 Long-Evans rats were dosed perinatally with 0 or 30.6 mg/kg/day of DE‑71from gestation day 6 through sampling on postnatal day 14. Proteins from the cerebellum and hippocampus were extracted, expression differences were detected by two-dimensional differencegel electrophoresis, and proteins were identified by tandem mass spectrometry. Protein networkinteraction analysis was performed using Ingenuity ® Pathway Analysis, and the proteins of interestwere validated by Western blotting.Results: Four proteins were significantly differentially expressed in the cerebellum followingDE‑71 exposure, whereas 70 proteins were significantly differentially expressed in thehippocampus. Of these proteins, 4 from the cerebellum and 47 from the hippocampus, identifiableby mass spectrometry, were found to have roles in mitochondrial energy metabolism, oxidativestress, apoptosis, calcium signaling, and growth of the nervous system.Conclusions: Results suggest that changes in energy metabolism and processes related toneuroplasticity and growth may be involved in the developmental neurotoxicity of PBDEs.