Application of Neurochemical Markers for Assessing Health Effects after Developmental Methylmercury and PCB Coexposure

E Roda,T Coccini,L Manzo

doi:10.1155/2012/216032

E Roda, T Coccini + Show 1 more

Open Access

https://doi.org/10.1155/2012/216032

Copy DOI

Abstract

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 0.1–36.78 fmol/million cells; MAO-B, 0.95–14.95 nmol/mg protein/h). No correlation was found between the two biomarkers and neurotoxicant concentrations in blood (pre- and postnatally).

Highlights

In the last few decades, the continuous exposure of humans to complex mixture of contaminating substances in food is an issue that has been giving increasing cause for concern
In a recent in vivo study, we demonstrated that perinatal exposure to MeHg (0.5 mg/kg/day) and/or PCB153 (5 mg/kg/day) given orally to rat dams, affected D1 and D2 receptors in a gender, time, and brain area-dependent fashion, without additive effects of the two chemical compounds when administrated in mixture [60]
The present study demonstrates in laboratory animals that developmental exposure to MeHg (1 mg/kg/day, GD7PND7) and PCB153 (20 mg/kg/day, GD10–GD16), alone and in mixture, affects selected endpoints of cholinergic and monoaminergic transmission, namely, cerebellar monoamine oxidase-B (MAO-B) activity and cerebellar and lymphocyte muscarinic receptors (MRs), both in dams and weaning rats, 3 weeks after cessation of maternal dosing

Summary

Introduction

In the last few decades, the continuous exposure of humans to complex mixture of contaminating substances in food is an issue that has been giving increasing cause for concern. Because human populations are often exposed to mixtures, as for MeHg and PCBs in food, raising questions about possible additive, synergistic, or antagonistic effects of the components [20], the potential of these pollutants to interact, and the valuation of their joint effects should be thoroughly investigated, even though it is extremely difficult in epidemiological studies To gain this goal, studies investigating biochemical parameters in accessible non-neural tissues, which are similar to those targeted by chemicals in the brain (see [21]), may represent a successful approach to developing markers of neurotoxicity, which could be useful in exposed people [22, 23]. In a second step, MRs in lymphocytes (lMRs) and MAO-B in platelets (p-MAO-B) have been applied in a selected human population, with the aim at supporting (i) the predictive value of these biomarkers and (ii) the relevance of a translational approach in environmental medicine

Experimental Protocols

Results

Lymphocytes MRs

Neurochemical Markers in Humans

Discussion