Developmental Exposure to Polychlorinated Biphenyls or Dioxin: Do Changes in Thyroid Function Mediate Effects on Spatial Learning?

Abstract

SYNOPSIS. Polychlorinated biphenyls (PCBs) and dioxins are widespread environmental contaminants that are suspected of causing cognitive deficits in children exposed in utero. Very little is known about which of the PCB and dioxin congeners present in the environment are responsible for the changes in cognitive function or about the mechanisms through which these chemicals affect the central nervous system (CNS). Because both PCBs and dioxins reduce circulating thyroid hormone levels, it has been proposed that these chemicals may affect CNS function indirectly by reducing the availability of thyroid hormone to the brain during development. Thyroid hormones play a critical role in brain development, and spatial learning and memory is one of the behavioral functions most severely affected by neonatal hypothyroidism. In the studies reviewed here, we investigated the effects of three ortAo-substituted PCBs, two coplanar PCBs and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on spatial learning and memory in the rat. Pups exposed to PCBs or TCDD in utero and during lactation were tested when they reached adulthood. All three ortAo-substituted PCBs caused deficits in spatial learning, but only two of the three reduced circulating thyroid hormone concentrations. Furthermore, the learning deficit was observed only in females, but thyroid hormones were equally depressed in males and females. Thus, the PCB-induced deficit in spatial learning did not appear to be mediated by the decreased thyroid hormone levels. TCDD and coplanar PCBs caused moderate reductions in thyroid hormone, but facilitated rather than impaired spatial learning, an effect that has been reported in neonatally /type/thyroid rats. The possibility that TCDD and coplanar PCBs may act as mixed thyroid agonists/antagonists causing hypothyroid-like effects in some tissues and hyperthyroid-like effects in other tissues is discussed.