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

Abstract

<jats:p>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.<jats:italic>Animal Data</jats:italic>. 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.<jats:italic>Human Data</jats:italic>. 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).</jats:p>

Canadian Arctic Contaminants and Their Effects on the Maternal Brain and Behaviour: A Scoping Review of the Animal Literature

“…Again, MR dissociation constants did not differ between groups. As well, monoamine oxidase B activity did not differ between the treatment groups and the control group [101]. 1 month prior to pairing until anticipated hatching of eggs 8% of PCB-exposed pairs abandoned their clutches prior to hatching.…”

“…Co-exposed groups had similar regional increases and decreases as the PCB-only exposed group. In a second study using the same dosing regimen, a higher dose of MeHg increased cerebellar MR density, but limited changes were observed with the other treatment groups [101].…”

“…Roda et al [101] used the same dosing regime as the above study to further investigate the potential role of alterations in the cholinergic systems as biomarkers for MeHg and PCB-associated neurotoxicity. In this experiment, dams exposed to the higher dose of MeHg expressed a significant increase in cerebellar MR density [101] (Table 3). Exposure to the lower dose of MeHg, PCB 153, and either MeHg dose in combination with PCB 153 did not result in significant MR density changes.…”

PCB95 and PCB153 change dopamine levels and turn-over in PC12 cells

“…We noticed that the levels of DOPAL, DOPAC and DOPET were elevated after 12 h exposure to PCB153 but not at 24 h exposure. In male rat brains at post-natal-day 21 MAO-B activity (scheme 1: J) in the cerebellum was shown to be significantly decreased, up to 45%, after exposure to PCB153 in utero (Roda et al , 2012). Although the methods in the cited study differed considerably from the present study, it may suggest a possible reason for the two phases, i.e.…”

Evaluation of alterations in dopamine and neuro-toxicity caused by co-exposure to lead (Pb) and polychlorinated biphenyls (PCBs)

“…We noticed that the levels of DOPET, L-DOPA and DOPAL increased after 12 h exposure but not at 24 h exposure. MAO-B activity was shown to be significantly, up to 45%, decreased in the cerebellum of male's rats exposed to PCB153 (Roda et al, 2012), however, that study cannot be compared to our study because it was in vivo, and at different conditions. Alternatively, VMAT2 inhibition causes elevated DA turnover through the enzymatic pathways.…”