Developmental polychlorinated biphenyl mixture exposure promotes selective neural alterations: An immunohistochemical study in adult rat offspring

The fetus and neonate are especially vulnerable to toxic effects of polychlorinated biphenyls (PCBs), that have been shown to perturb behavioral and neuropsychological development. This study aimed to examine the long-term effects of developmental exposure to PCBs. Doses selected were environmentally relevant to those found in epidemiological studies, on the central nervous system (CNS) of adult rat offspring. Pregnant Sprague Dawley rats were fed cookies that contained a mixture of fourteen PCBs or vehicle (corn oil) daily. PCB doses were 0.011 mg/kg maternal body weight/day ("low") or 1.10 mg/kg maternal body weight/day ("high"), for 42 days throughout gestation and lactation. Adult offspring were euthanized on postnatal day 450. A battery of immunohistochemical markers of brain structure and function were selected to assess possible effects of developmental PCB exposure. Using a 3×2 factorial design (treatment and sex), two-way analysis of variance revealed significant effects of treatment through the CNS, with no main effect of sex or interaction effects. In comparison with controls, both low and high dose developmental PCB exposure significantly (<i>p</i> < 0.05) increased inhibitory enzyme glutamic acid decarboxylase (GAD67) immunoreactivity in the cerebellar vermis, and decreased lipofuscin autofluorescence in the locus coeruleus (LC). Low dose developmental PCB exposure significantly decreased the perimeter of endothelial cells in the periaqueductal gray, ventral orbitofrontal cortex; and decreased lipofuscin in the dorsal striatum, compared to controls. Findings support the Developmental Origins of Health and Disease concept, which broadly posits that early-life perturbations may influence health trajectories over the lifespan.