Sex-specific effects of developmental exposure to polychlorinated biphenyls on neuroimmune and dopaminergic endpoints in adolescent rats

Abstract

Exposure to environmental contaminants early in life can have long lasting consequences for physiological function. Polychlorinated biphenyls (PCBs) are a group of ubiquitous contaminants that perturb endocrine signaling and have been associated with altered immune function in children. In this study, we examined the effects of developmental exposure to PCBs on neuroimmune responses to an inflammatory challenge during adolescence. Sprague Dawley rat dams were exposed to a PCB mixture (Aroclor 1242, 1248, 1254, 1:1:1, 20 μg/kg/day) or oil control throughout pregnancy, and adolescent male and female offspring were injected with lipopolysaccharide (LPS, 50 μg/kg, ip) or saline control prior to euthanasia. Gene expression profiling was conducted in the hypothalamus, prefrontal cortex, striatum, and midbrain. In the hypothalamus, PCBs increased expression of genes involved in neuroimmune function, including those within the nuclear factor kappa b (NF-κB) complex, independent of LPS challenge. PCB exposure also increased expression of receptors for dopamine, serotonin, and estrogen in this region. In contrast, in the prefrontal cortex, PCB exposure blunted or induced irregular neuroimmune gene expression responses to LPS challenge. Moreover, neither PCB nor LPS exposure altered expression of neurotransmitter receptors throughout the mesocorticolimbic circuit. Almost all effects were present in males but not females, in agreement with the idea that male neuroimmune cells are more sensitive to perturbation and emphasizing the importance of studying both male and female subjects. Given that altered neuroimmune signaling has been implicated in mental health and substance abuse disorders that often begin during adolescence, these results highlight neuroimmune processes as another mechanism by which early life PCBs can alter brain function later in life.