Coplanar PCB Congeners Increase Uterine Weight and Frontal Cortical Dopamine in the Developing Rat: Implications for Developmental Neurotoxicity

Abstract

We show that developmental exposure of the laboratory rat to the coplanar polychlorinated biphenyl (PCB) congener 3,4,3',4'-tetrachlorobiphenyl (TCB) and the structurally similar congener 3,4,5,3',4'-pentachlorobiphenyl (PtCB) elevates dopamine (DA) concentrations in the prefrontal cortex (PFC). To determine whether these coplanar congeners are estrogenic, and may thus contribute to the elevations in PFC DA, we measured uterine wet weight (UWW) in prepubertal rats exposed to TCB or PtCB. For comparison, additional animals were exposed to either the ortho-substituted congener 2,4,2',4'-tetrachlorobiphenyl (o-TCB) or 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), a coplanar congener highly resistant to metabolism. Both TCB and PtCB increased UWW, but this effect was blocked after exposure to the anti-estrogen ICI 182,780. Neither o-TCB nor HCB altered UWW. These results demonstrate that certain coplanar PCB congeners and/or their metabolites, are estrogenic, and suggest that exposure during critical periods of neuronal development may increase central DA concentrations, and by inference, alter behavior.

Oral administration of PCBs induces proinflammatory and prometastatic responses

“…They exert Due to their stability and lipophilic character, PCBs persist in the environment and accumulate in fatty tissues of animals and humans (Kimbrough, 1995;Hansen, 1999). PCBs are well known as potential neurotoxic (Seegal et al, 2005), teratogenic, and embriotoxic agents, effecting the embryonic development in fish (Arzuaga et al, 2004), birds (Hoffman et al, 1996;Summer et al, 1996), rodents (Goodwill et al, 2007; Kimura- Kuroda et al, 2007) and humans (Pocar et al, 2006;Roegge and Schantz 2006). PCBs can also contribute to the development of cancer in experimental animals (Carpenter, 2006;Knerr and Schrenk, 2006;Lehmann et al, 2007) and are classified as the probable carcinogens in humans (class 2A carcinogens according to the IARC classification) (Shields, 2006).…”

Ontogenetic Alterations in Molecular and Structural Correlates of Dendritic Growth after Developmental Exposure to Polychlorinated Biphenyls

“…In cultured neurons, PCBs alter intracellular calcium and protein kinase C signaling [reviewed by Kodavanti (2005)], whereas in vivo PCB exposure transiently depletes dopamine levels (Seegal 1996), alters circulating estrogen levels and estrogen-related functions (Kaya et al 2002; Seegal et al 2005), and interferes with thyroid hormone signaling via both thyroid hormone receptor-dependent (Bogazzi et al 2003; Kitamura et al 2005; Miyazaki et al 2004) and-independent (Bansal et al 2005; Zoeller et al 2000) mechanisms. That PCBs may alter dendritogenesis is further suggested by recent reports that hydroxylated PCB metabolites inhibit thyroid hormone-dependent dendritic growth in primary cultures of mouse cerebellar Purkinje cells (Kimura-Kuroda et al 2005).…”

Differential neurotoxic effects of <i>in utero</i> and lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) on spontaneous locomotor activity and motor coordination in young adult male mice

“…In addition, hyperactivity in the home cage during the dark phase was correlated with an elevation in dopamine levels in the striatum (Decker et al, 2005). Perinatal and subchronic exposure to some PCB congeners and OH-PCB 106 induced alterations in the dopaminergic nervous system in rodents (Caudle et al, 2006;Faroon et al, 2000;Lee et al, 2012;Lesmana et al, 2014;Seegal et al, 2005). The results from this study, therefore, suggest that hyperactivity of mice exposed to OH-PCB 106 in utero in the home cage during the dark phase may be caused by the disruption of the dopaminergic nervous system.…”