Bioaccumulation and behavioral effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in perinatally exposed mice

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants that have become pervasive environmental contaminants and may contribute to adverse health outcomes. We evaluated in mice the developmental neurotoxicity of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), one of the most abundant PBDE congeners detected in animal and human tissues. Female C57BL/6J mice were exposed to daily doses of 0, 0.03, 0.1 or 1 mg/kg beginning 4 weeks prior to conception, continuing through gestation and lactation, and ending at weaning on postnatal day (PND) 21. Levels of BDE-47 in blood, brain, liver and adipose tissues of dams were markedly increased after 4 weeks of exposure, around the time of mating, and continued to increase through the time of parturition. Blood levels of BDE-47 in the dosed dams were within the range reported in humans. BDE-47 tissue levels in the dams decreased between parturition and weaning, possibly reflecting mobilization during lactation. Brain BDE-47 levels in the offspring at PND 1 approached those of the dams at parturition. Perinatal exposure to BDE-47 resulted in significant dose dependent growth retardation, slower motor performance in several behavioral tests, and mice exposed to 1 mg/kg/day BDE-47 showed altered performance in the Morris water maze. There were no differences between groups in the numbers of pyramidal neurons in hippocampus CA1. These results document accumulation of BDE-47 in several organ systems following exposure to low-levels of BDE-47, and provide evidence that such exposure is associated with early behavioral deficits in exposed neonates.     

The effect of thiamin tetrahydrofurfuryl disulfide on behavior of juvenile DBA/2J mice

Due to genetic defects or illness some individuals require higher amounts of thiamin than are typically provided by the diet. Lipid-soluble thiamin precursors can achieve high blood levels of thiamin and result in increased concentrations in the central nervous system. High intakes of thiamin have been reported as beneficial in children with autism and attention deficit/hyperactivity disorder. The current study examined the effect of thiamin tetrahydrofurfuryl disulfide (TTFD), a lipophilic precursor, on behavior in the juvenile male DBA/2J mouse. Mice given by oral gavage deionized water or deionized water providing 100 mg or 340 mg TTFD/kg body weight daily for 17 d, starting at postnatal day 18, were tested for effects on operant learning, social interaction, general activity level, and prepulse inhibition of acoustic startle, as well as effects on growth and select organ weights. Results indicate lower activity and altered social interaction at both treatment levels and decreased acoustic startle at the 100 mg/kg level. Compared to controls, percent weight gain was lower in the TTFD-treatment groups, but percent body length increase was not affected by TTFD treatment. TTFD treatment did not influence percent organ weights as percentage of body weights. TTFD treatment resulted in increased whole brain thiamin concentrations. These results support the concept that lipophilic thiamin precursors provided during early development can affect a number of behavioral parameters. In clinical trials with children with behavior disorders, attention should be given to preventing possible adverse gastrointestinal irritant effects associated with TTFD therapy.