Developmental Neurotoxicity in Mice Neonatally Co-exposed to Environmental Agents : PCB, PBDE, Methyl Mercury and Ionized Radiation - Interactions and Effects

This thesis investigates the neurotoxic effects in mice neonatally co-exposed to different toxic environmental agents during a defined critical period of the brains's rapid growth and development. Environmental toxic agents are incorporated in our environment. The agents investigated in this thesis are ortho-substituted polychlorinated biphenyls (PCBs 52, and 153), co-planar PCB (PCB 126), polybrominated diphenyl ether (PBDE 99), methyl mercury (MeHg), and γ-radiation. Several epidemiological studies show that human exposure to environmental agents during early development can affect childhood cognitive development. The brain growth spurt (BGS) is defined by rapid growth and development of the immature brain. For rodents (rats and mice) the BGS is postnatal spanning the first 3-4 weeks after birth. For humans this period begins during the third trimester of pregnancy and continues throughout the first two years of life. Several studies have shown that the BGS period of the brain's development renders the brain vunerable and susceptible to insults caused by environmental agents. The combinations of environmental agents used in this thesis were: PCB 52 + PBDE 99, PCB 153 + MeHg, PCB 126 + MeHg, PBDE 99 + MeHg, and γ-radiation + MeHg. The studies presented in this thesis show that co-exposure to low doses of environmental agents lead to interaction effects. These effects of interaction include defective spontaneous behavior, diminished habituation capabilities and hyperactive condition, decreased learning and memory abilities, and reduction in the nicotinic cholinergic receptor densities. Traditionally environmental agents are evaluated one at a time to investigate their effects of toxicity. This thesis indicates that the effects of interaction caused by co-exposure were often seen at doses where exposure to the individual environmental agent alone did not cause any effect. The observed effect of co-exposure were often as pronounced as a dose up to ten times the individual environmental agent alone