Mechanisms involved in the neurotoxic effects of environmental toxicants such as polychlorinated biphenyls and brominated flame retardants

Abstract

Many toxic substances have been distributed to the environment, some of which have properties that promote accumulation and biomagnification in living organisms. Approximately 1.2 million metric tons of polychlorinated biphenyls (PCBs) have been produced and about 30% have been discharged to the environment. Approximately 200 000 metric tons of brominated flame retardants (BFRs) are produced annually, of which considerable amounts have been spread globally, even to the Polar Regions. Behavioral testing of animals has shown that these compounds may affect learning, memory and fine motor functions. Animals are most sensitive during early development. Several epidemiological studies have shown that PCBs and BFRs may be responsible for similar effects in humans. Of especially concern are possible effects of PCBs and BFRs in mixtures containing the highly neurotoxic methyl mercury. The compounds affect several targets in the nervous system that seem to be interconnected, and may be responsible for the observed behavioral deficits. It was shown early that PCBs affect dopamine and serotonin levels in the brain. Later studies showed that transport mechanisms of these neurotransmitters appear to be particularly sensitive to PCBs. Furthermore, PCBs affect intracellular calcium levels and induce formation of reactive oxygen species both in vivo and in vitro, and reduce cell viability in vitro. Neuroendocrine functions, particularly the thyroid hormone system, are also sensitive to disruption by PCBs and BFRs. Their metabolites, such as hydroxy-metabolites, appear to be particularly potent. We conclude that PCBs are particularly toxic during early development and that the toxic effects are a combination of several factors, including disturbance of calcium homeostasis, oxidative stress, and influence on neurotransmitter transport. Monoaminergic cells appear to be particularly vulnerable.