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

ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are structurally similar to polychlorinated 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.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.Pregnant Long-Evans rats were dosed perinatally with 0 or 30.6 mg/kg/day of DE-71 from gestation day 6 through sampling on postnatal day 14. Proteins from the cerebellum and hippocampus were extracted, expression differences were detected by two-dimensional difference gel electrophoresis, and proteins were identified by tandem mass spectrometry. Protein network interaction analysis was performed using Ingenuity® Pathway Analysis, and the proteins of interest were validated by Western blotting.Four proteins were significantly differentially expressed in the cerebellum following DE-71 exposure, whereas 70 proteins were significantly differentially expressed in the hippocampus. Of these proteins, 4 from the cerebellum and 47 from the hippocampus, identifiable by mass spectrometry, were found to have roles in mitochondrial energy metabolism, oxidative stress, apoptosis, calcium signaling, and growth of the nervous system.Results suggest that changes in energy metabolism and processes related to neuroplasticity and growth may be involved in the developmental neurotoxicity of PBDEs.

SUBMITTER: Kodavanti PR

PROVIDER: S-EPMC4421769 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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

Kodavanti Prasada Rao S PR Royland Joyce E JE Osorio Cristina C Winnik Witold M WM Ortiz Pedro P Lei Lei L Ramabhadran Ram R Alzate Oscar O

Environmental health perspectives 20141219 5

<h4>Background</h4>Polybrominated diphenyl ethers (PBDEs) are structurally similar to polychlorinated 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 tr ...[more]

PMID: 25616259

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Project description:BackgroundIn the United States, one in six children are affected by neurodevelopmental disorders, and polybrominated diphenyl ethers (PBDEs) in flame-retardant chemicals are measured ubiquitously in children.ObjectiveWe conducted a systematic a systematic review regarding developmental exposure to PBDEs and intelligence or Attention Deficit/Hyperactivity Disorder (ADHD) and attention-related behavioral conditions in humans.MethodsWe searched articles published up to 26 September 2016, and included original studies that quantified exposures to PBDEs incurred any time in proximity to conception or during in utero, perinatal, or childhood time periods. We evaluated the risk of bias of individual studies and the overall quality and strength of the evidence according to the Navigation Guide systematic review methodology. We established criteria in advance to identify studies that could be combined using random effects meta-analyses (DerSimonian-Laird method).ResultsFifteen studies met the inclusion criteria; 10 studies met the criteria for intelligence and nine for attention-related problems. We rated studies generally with "low" to "probably low" risk of bias and rated the overall body of evidence as "moderate" quality with "sufficient" evidence for an association between Intelligence Quotient (IQ) and PBDEs. Our meta-analysis of four studies estimated a 10-fold increase (in other words, times 10) in PBDE exposure associated with a decrement of 3.70 IQ points (95% confidence interval: 0.83, 6.56). We concluded the body of evidence was of "moderate" quality for ADHD with "limited" evidence for an association with PBDEs, based on the heterogeneity of association estimates reported by a small number of studies and the fact that chance, bias, and confounding could not be ruled out with reasonable confidence.ConclusionWe concluded there was sufficient evidence supporting an association between developmental PBDE exposure and reduced IQ. Preventing developmental exposure to PBDEs could help prevent loss of human intelligence. https://doi.org/10.1289/EHP1632.

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

Publications

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

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