Assessment of the neurotoxic mechanisms of decabrominated diphenyl ether (PBDE-209) in primary cultured neonatal rat hippocampal neurons includes alterations in second messenger signaling and oxidative stress

Toxicol Lett. 2010 Feb 15;192(3):431-9. doi: 10.1016/j.toxlet.2009.11.020. Epub 2009 Dec 3.

Abstract

2',2',3',3',4',4',5',5',6',6',-decabrominated diphenyl ether (PBDE-209) is the most widely used polybrominated diphenyl ethers (PBDEs) globally. Some animal experiments have found that PBDE-209 caused developmental neurotoxicity. But detailed mechanisms are less well understood. Our experiments were conducted to research the potential neurotoxic mechanisms of PBDE-209 in primary cultured neonatal rat hippocampal neurons by measuring cell viability, apoptotic rate, expression of P38 mitogen-activated protein kinases (MAPKs), calcium ion concentration, oxidative stress, nitrous oxide (NO) content, and global gene DNA methylation levels. The neurons were exposed to different PBDE-209 concentrations (0, 10, 30 and 50 microg/ml). The difference between the experimental groups and control groups was significant (P<0.05). PBDE-209 increased the rate of apoptosis, expression of P38 MAPK, calcium ion concentration, reactive oxygen species (ROS) level, malondialdehyde (MDA) content and NO content (P<0.05). In addition, PBDE-209 deceased cell viability, activity of superoxide dismutase (SOD) and the levels of global gene DNA methylation (P<0.05). The results suggested that PBDE-209 could affect secondary messengers, cause oxidative stress and decrease global gene DNA methylation levels. These actions may contribute to the mechanism of PBDE-209 neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Calcium / analysis
  • Cell Survival / drug effects
  • Cells, Cultured
  • Flow Cytometry
  • Halogenated Diphenyl Ethers / pharmacology*
  • Hippocampus / chemistry
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Malondialdehyde / analysis
  • Neurons / drug effects
  • Neurons / metabolism
  • Nitrous Oxide / analysis
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / analysis
  • Second Messenger Systems / drug effects*
  • Superoxide Dismutase / drug effects
  • p38 Mitogen-Activated Protein Kinases / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / drug effects

Substances

  • Halogenated Diphenyl Ethers
  • Reactive Oxygen Species
  • Malondialdehyde
  • Superoxide Dismutase
  • p38 Mitogen-Activated Protein Kinases
  • Nitrous Oxide
  • decabromobiphenyl ether
  • Calcium