Study of Polychlorinated Biphenyls as Potential Modifiers of Developmental Neurotoxicity of Methylmercury

The developing brain is the most susceptible target for methylmercury (MeHg) toxicity. Typical features of developmental MeHg neurotoxicity include the delayed onset of symptoms and the persistency of dysfunction. One of the factors which may modulate MeHg neurotoxicity is co-exposure to other neurotoxic pollutant, e.g. polychlorinated biphenyls (PCBs) from the same dietary sources. Because PCBs themselves can induce subtle neurodevelopmental deficiencies, recent epidemiological and research studies have focused on the potential hazard resulting from mixtures of PCBs and MeHg. This work summarizes our experimental findings on several endpoints of the cholinergic and aminergic systems in the developing rat brain, following two distinct perinatal co-exposure protocols involving low to moderate doses of MeHg and PCB153 or PCB126. The neurochemical modifications induced by either agent, alone or combined, involved monoamineoxidase type-B activity, biogenic amine levels (e.g., serotonin and dopamine), total cholinergic muscarinic receptors (MRs) and M1, M2 and M3 subtypes. The effects were brain region-, age- and gender-dependent. Some early-onset changes (weaning) persisted until puberty, while other alterations became manifest only at the advanced time point, when the brain levels of Hg, PCB153, and PCB126 had declined. The results of the combined exposure ruled out synergistic interactions between MeHg and PCB153 or PCB126 on every neurochemical endpoint tested. This applied to all pups regardless of the (i) regimen of exposure, (ii) gender, (iii) age, and (iv) brain area. The co-treatment with either PCB153 or PCB126 sometimes masked MeHg-induced changes on selected neurochemical endpoints. Nevertheless, this cannot be viewed as a protective effect. The final health effect may be masked at early time-points, but may become manifest later during life time.

COCCINI Teresa;  CASTOLDI Anna;  RODA Elisa;  SARIGIANNIS Dimosthenis;  MANZO Luigi; 

2009-02-13

PARLAR SCIENTIFIC PUBLICATIONS (P S P)

JRC45634

1018-4619,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC45634,