Perinatal co-exposure to methylmercury and PCB 153 or PCB 126 in rats alters the cerebral cholinergic muscarinic receptors at weaning and puberty

In the last few decades, combined exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) from fish and seafood, and their potentially interactive effects on neurodevelopment, have been giving increasing cause for concern. We examined the combined effects of MeHg and either a non-dioxin PCB (PCB 153) or a dioxin-like PCB (PCB 126) congener on the developing brain cholinergic muscarinic receptors (MRs). These receptors are known to play a major role in many central functions including higher cognitive processes and the modulation of extrapyramidal motor activity. MRs in pup rat brains diminished following prenatal and lactational exposure, from gestational day [GD]7 to postnatal day [PND]2 1, to MeHg (0.5 mg/kg body weight [bw]/day), PCB 153 (5 mg/Kg bw/day), and PCB 126 (100 ng/kg/day), alone or in combination. Total MR density, as well as M I, M2, and M3 receptor subtypes of the weanling and pubertal rats, were affected in a brain-area-, gender-, time- and compound-dependent fashion. MeHg decreased (by 15-20%) the total MR density in a delayed (PND36) manner in the cerebral cortex of both genders, and early (at weaning) in the cerebellum of both genders, with the effect lasting until puberty (in males only). MeHg decreased the ACh Ml- and M3-immunopositive neurons in the cerebral cortex and also increased the M2-immunopositive Bergmann glia in the cerebellum. PCB 153 also induced a delayed (PND36) decrease (of 20%) in total MR number in the cerebellum of the male offspring and in the cerebral cortex of both genders. The latter effect was coupled with a decrease in ACh M I - and ACh M3-immunopositive neuron populations. PCB 126 decreased (by 30-40%) total MR density in a gender-dependent manner, males being more sensitive than females. The effect was evident early (at PND2 1) and lasted until puberty in the cerebellum, while it was observed later (at PND36) in the cerebral cortex. The M I and M3 receptors were similarly affected by PCB 126. Co-exposure to MeHg and either PCB 153 or PCB 126 had the same effect on the cerebral MRs as exposure to each compound alone. The results rule out additive or synergistic interactions between MeHg and PCB153 or PCB126 on MRs in the brain areas examined.