Neonatal Exposure to Highly Brominated Diphenyl Ethers and Perfluorinated Compounds : Developmental Dependent Toxicity and Interaction
Abstract: This thesis investigated the developmental neurotoxic effects of neonatal exposure to highly brominated diphenyl ethers (PBDEs) and perfluorinated compounds (PFCs), alone or in combinations, during a critical period of the brains’ rapid growth and development, in mice. The compounds investigated were the decaBDE (PBDE 209), nonaBDE (PBDE 206), octaBDE (PBDE 203), heptaBDE (PBDE 183), and three PFCs, PFOS, PFOA, and PFDA.PBDEs and PFCs have been identified as emerging classes of persistent environmental compounds, present in wildlife as well as humans, and present at higher levels in infants/children, compared to older persons. Individuals can be exposed to these compounds throughout her/his lifetime and newborn/children can be exposed to toxicants both via the mothers’ milk and directly via ingestion and inhalation.The brain growth spurt (BGS) is defined by rapid growth and developmental of the brain. For rodents (mice and rats), the BGS is postnatal spanning the first 3-4 weeks after birth. In humans this period begins during the third trimester of pregnancy and continues throughout the first two years of life. It has been shown that several environmental toxicants can induce permanent disorders in brain function when administered to the neonatal mouse, during the BGS.This thesis shows that highly brominated PBDEs, including PBDE 209, PBDE 206, and PBDE 203 can cause developmental neurotoxic effects, when given directly to the neonatal mouse. Of the investigated PFCs, PFOS and PFOA were shown to cause similar effects as the PBDEs. Furthermore, PBDE 209 and PFOA can at low doses interact and enhance the neurotoxic effects in mice. Effects in the adult animal included; deranged spontaneous behavior, reduced or lack of habituation, decreased learning and memory abilities, and increased susceptibility of the cholinergic system. Both classes of compounds were shown to affect proteins (CaMKII, GAP-43, synaptophysin, and tau) important for neuronal growth and synaptogenesis in the neonatal mouse brain.
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