Perinatal co-exposure to methylmercury and PCB153 or PCB126 in rats alters the cerebral cholinergic muscarinic receptors at weaning and puberty (original) (raw)
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NeuroToxicology, 2006
The developing nervous system is thought to be particularly sensitive to polychlorinated biphenyls (PCBs) present as food contaminants together with methylmercury (MeHg). Effects of perinatal co-exposure to PCB153 and MeHg on brain cholinergic muscarinic receptors (MRs) were investigated by saturation binding studies in mature and immature rats. MeHg alone (1 mg/kg/day, GD7-PND7) enhanced cerebral MRs more in dams (87% and 60% in cerebellum and cerebral cortex, respectively) than in PND21 pups (0-50%) in accordance with the higher Hg levels detected in the adult brain (7-9 mg/g) than in the male and female offspring's brain (1.5-2.8 mg/g). Prenatal administration of PCB153 (20 mg/kg/ day, GD10-GD16), leading to higher contaminant levels in the offspring brain than in that of adults (25-66 mg/g versus 3 mg/g), induced cerebral MR changes of similar extent at both ages, namely decreased cerebellar (20-30%) and increased cortical MR density (40-50%). Co-exposure to PCB and MeHg had no more effect than exposure to either compound alone on cerebral cortex MRs, whereas, in the cerebellum, the combined treatment induced a PCB-like lowering of the MR density that masked the MeHg-induced receptor increase. None of the treatments affected the striatal and hippocampal MRs. A lower MeHg dose (0.5 mg/kg/day) was without any effect on cerebral MRs. These results show that MRs are one of the sensitive biochemical endpoints of the central nervous system altered by developmental exposure to MeHg and PCB153. Cerebral cortex and cerebellum were the most susceptible targets in the response to these neurotoxicants. MR changes were detected in both immature and adult animals and the interaction of MeHg and PCB153 at the level of these receptors occurred in a non-additive manner. #
International journal of occupational medicine and environmental health, 2009
Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants. Both are neurotoxic, especially for the developing brain. The main source of human exposure to MeHg and PCBs is seafood. The aim of the present work was to find out whether and how separate or combined perinatal exposure to these neurotoxicants affects neurobehavioural functions in maturity. The study was performed on adult Wistar rats, the progeny of rat mothers exposed to MeHg (0.5 mg/kg/day or 2.0 mg/kg/day), PCB 153 (1.0 mg/kg/day or 5.0 mg/kg/day), or to MeHg 0.5 mg/kg/day + PCB 153 5.0 mg/kg/day, from day 7 of pregnancy to day 21 post partum. The following functions were assessed: spontaneous locomotor activity (open field test), spatial short-term memory (radial maze test), long-term memory (passive avoidance test), sensitivity to pain and vulnerability to stress (hot plate test), efficiency of the sensorimotor gating (startle response test), and sensorimotor coordination (the r...
2006
The individual and joint effects of methylmercury (MeHg; 1 mg/kg body weight/day, GD7-PND7) and PCB153 (20 mg/kg body weight/day, GD10-GD16), administered orally to rat dams, were explored in 21-day-old rat offspring brain in terms of monoamine oxidase B (MAO-B) activity and regional content of dopamine (DA), serotonin (5-HT), 5-hydroxy-indole-3-acetic acid (5-HIAA) and homovanillic acid (HVA). Neither treatment altered MAO-B in striatum, hippocampus, cerebellum and cerebral cortex of female pups. In males the cerebellum displayed a significantly reduced enzyme activity (25-45%) following all treatments.
Journal of toxicology, 2012
Cholinergic muscarinic receptors (MRs) and monoamine oxidase activity (MAO-B), expressed both in brain and blood cells, were investigated in animals and exposed subjects to assess (i) MeHg (0.5-1 mg/kg/day GD7-PD7) and/or PCB153 (20 mg/kg/day GD10-GD16) effects on cerebellar MAO-B and MRs, and lymphocyte MRs, in dams and offspring 21 days postpartum; (ii) MAO-B in platelets and MRs in lymphocytes of a Faroese 7-year-old children cohort, prenatally exposed to MeHg/PCBs. Animal Data. MAO-B was altered in male cerebellum by MeHg, PCB153, and their combination (35%, 45%, and 25% decrease, resp.). Cerebellar MRs were enhanced by MeHg alone in dams (87%) and male pups (27%). PCB153 alone and in mixture did not modify cerebellar MRs. Similarly to brain, lymphocyte MRs were enhanced in both dams and offspring by MeHg alone. All changes were caused by 1 MeHg mg/kg/day, the lower dose was ineffective. Human Data. Both biomarkers showed homogeneous distributions within the cohort (MRs, range 0...
Environmental Toxicology and Pharmacology, 2008
Epidemiological and laboratory studies have suggested that polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) may have additive or synergistic effects on CNS function. Aim of this study was to characterize the effects of exposure to low levels of MeHg (0.5 mg/kg day in drinking water) and PCB126 (100 ng/kg day in food), alone and in combination, on neurobehavioral development in Wistar rats. Dams were treated from gestational day 7 to post-natal day (PND) 21. Animals were tested for developmental landmarks and reflexes (PND1-21), attention deficits (PND40), locomotor activity (PND30, 110), spatial learning (PND75), coordination and balance (PND90), object discrimination (PND80), anxiety (PND100), and conditioned learning (PND110). Parameters related to pregnancy, sex ratio at birth, and physical development (at weaning) did not differ among groups, though PCB126 decreased number of pups at birth. A slight delay in negative geotaxis was found in female rats in all treatment groups. No significant effects were seen in attention, coordination and balance, object discrimination, and spatial and conditioned learning. Increased motor activity was present in PCB126-treated male and in MeHg + PCB-treated female rats in the elevated plus maze test, and in PCB126-treated male rats in the open field test (PND110). The results do not support the hypothesis that co-exposure to MeHg and PCB126 results in additive or synergistic effects. This finding is in agreement with more recent in vitro and in vivo studies.
Fundamental Toxicological Sciences, 2015
While the primary source of human MeHg exposure is the consumption of fish contaminated with MeHg, it is unknown whether the toxicity of MeHg in fish is equivalent to that of MeHg chloride (MeHgCl) experimentally added to the diet. We investigated developmental and behavioral effects of MeHg derived from fish and MeHgCl added to various diets during the prenatal period in mice from GD 0 to GD 17. From 7 to 9 female C57BL/6NCr mice were assigned to each of the following exposure groups: Control (CL), CL+MeHgCl (CL+MeHg, 1.6 mgHg/kg), low MeHg tuna (LT, 0.2 mgHg/kg), LT+MeHgCl (LT+MeHg, 1.6 mgHg/kg), and high MeHg tuna (HT, 1.6 mgHg/kg). In pups, body weight was depressed and elevated by MeHg exposure in the CL+MeHg and the LT, respectively, compared with other three groups. In neurodevelopmental test, the righting reflex of 4 groups other than CL showed the facilitated developments compared to the CL. The cliff avoidance of the HT developed slower than in the CL+MeHg, LT and LT+MeHg. In water maze test, the swimming speed of the HT decreased in comparison with the CL in males but not females. The latency until falling from a rotating rod of the LT+MeHg was significantly shorter than that of the LT in males but not females. Our results are suggesting the possibility that the toxicological profiles of MeHg derived from fish and reagent MeHg are somewhat different. Our findings also provide evidence that males are more susceptible than females to prenatal MeHg exposure.
—Prenatal exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg) contaminated food may affect brain development, leading to long-term alterations in cognitive function. Both types of contaminants, PCBs and MeHg, are often found together contaminating food, especially fish in some polluted areas. Exposure to combinations of neurotoxicants may exert different effects on the developing nervous system than exposure to individual contaminants. Developmental exposure (during pregnancy and lac-tation) to PCB126 or PCB153 impairs learning ability when the rats are 3 months old. Impairment of learning seems to be a consequence of impairment of the function of the glutam-ate–nitric oxide (NO)– cGMP pathway in brain in vivo. The aims of the present work were 1) to assess whether perinatal exposure to MeHg also affects the function of the glutamate– NO– cGMP pathway in brain in vivo analyzed by in vivo brain microdialysis and/or the ability to learn the Y maze task when the rats are 3 months old, and 2) to assess whether perinatal exposure to combinations of MeHg with PCB153 or PCB126 potentiates, decreases or does not modify the effects of the individual neurotoxicants. Perinatal exposure to PCB126, PCB153 or MeHg impaired the function of the glutamate–NO– cGMP pathway in cerebellum and learning ability. However, co-exposure to PCB126MeHg or PCB153MeHg inhibits the impairment of the pathway or learning ability. These results support that the function of this pathway modulates learning of the Y maze task. Moreover, they show that co-exposure to these PCBs and MeHg does not exacerbate, but reduces the effects on the ability to learn this task.