Cross-omics gene and protein expression profiling in juvenile female mice highlights disruption of calcium and zinc signalling in the brain following dietary exposure to CB-153, BDE-47, HBCD or TCDD

Toxicology. 2014 Jul 3;321:1-12. doi: 10.1016/j.tox.2014.03.006. Epub 2014 Mar 27.

Abstract

The present study assessed if eating a diet of fish, spiked with persistent organic pollutants (POPs), affects gene and protein expression in the maturing mouse brain. Juvenile female Balb/c mice (22 days of age) were exposed for 28 days to fish-based diets spiked with the dioxin 2,3,7,8-tetrachlorodibenzodioxin (TCDD) or the non dioxin-like (NDL) chemicals hexabromocyclodocecane (HBCD), 2,2'4,4'-tetrabromodiphenylether (BDE-47) or 2,2'4,4',5,5'-hexachlorobiphenyl (CB-153) at doses approximating their respective lowest observed adverse effect levels (LOAEL). It was found that all POPs elicited changes in neural gene and protein expression profiles. Bioinformatic analysis of gene expression data highlighted the importance of the aryl hydrocarbon receptor (AHR) in dioxin toxicity and revealed that zinc regulation in the brain is targeted by TCDD through the AHR. Calcium homeostasis was affected by both TCDD and the NDL chemicals. In contrast to the transcriptomic analysis, the proteomics data did not allow for a clear distinction between DL and NDL responses in the juvenile brain but indicated that proteins associated with excitotoxicity were affected in all exposure groups. Integrated interpretation of data led to the conclusion that the dietary contaminants investigated in the present study breach the blood brain barrier (BBB) and accumulate in the juvenile brain where they may induce excitotoxic insults by dysregulation of the otherwise tightly controlled homeostasis of calcium and zinc. Overall, the findings of the present study highlight the need for further assessment of the risks associated with early life exposure to foodborne POPs.

Keywords: Dietary exposure; Gene expression; Juvenile brain; Persistent organic pollutants; Protein expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Brain Chemistry / drug effects
  • Brain Chemistry / genetics
  • Calcium Signaling / drug effects*
  • Diet
  • Environmental Pollutants / toxicity*
  • Female
  • Flame Retardants / toxicity*
  • Gene Expression Profiling
  • Genomics
  • Halogenated Diphenyl Ethers / pharmacology*
  • Hydrocarbons, Brominated / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Polychlorinated Biphenyls / pharmacology*
  • Polychlorinated Dibenzodioxins / pharmacology*
  • Pregnancy
  • Proteomics
  • RNA / biosynthesis
  • RNA / isolation & purification
  • Signal Transduction / drug effects*
  • Transcription, Genetic / drug effects
  • Zinc / physiology*

Substances

  • Environmental Pollutants
  • Flame Retardants
  • Halogenated Diphenyl Ethers
  • Hydrocarbons, Brominated
  • Polychlorinated Dibenzodioxins
  • 2,2',4,4'-tetrabromodiphenyl ether
  • hexabromocyclododecane
  • RNA
  • Polychlorinated Biphenyls
  • Zinc
  • 2,4,5,2',4',5'-hexachlorobiphenyl