Developmental neurotoxicity of polybrominated diphenyl ethers mixture de71 in Sprague-Dawley rats

Polybrominated diphenyl ethers (PBDE) are a class of brominated flame retardants that are recognized as global environmental contaminants and a potential adverse health risk. The objective of this study was to evaluate the developmental impacts on rat Sprague-Dawley (SD) pups at postnatal day (PND) 11, 21, 50, 105, and 250 after perinatal exposure to a DE71 mixture. These PNDs corresponded to juveniles, young, and mature adults, respectively. The analysis included histopathological, transcriptional evaluation, and Western blots in both hippocampus and midbrain. There were no marked histopathological changes, but significant transcriptional alterations were observed at PND 21 and 250 in midbrain. These changes occurred in a number of the markers of the cholinergic system, including acetylcholinesterase, muscarinic and nicotinic receptors, and structural gene,s including those of neurofilaments, cell adhesion molecules including N-cadherin and CAMKII, and cytokines. The markers were upregulated at least twofold or greater at PND 21. These biomarkers were predominantly altered in males at low dose (0.3 mg/kg), whereas females were affected only at high concentration (30 mg/kg). At PND 250 both males and females showed downregulation of markers in both intermediate- and high-dose groups. Our results support the findings that in utero and lactational exposure to DE71 mixture leads to transcriptional alterations in midbrain of adult SD rats.