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

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).

Figure 1

Histograms showing cerebellar MAO-B activity (a) and MRs binding in cerebellum (b1) and lymphocytes (b2) of both dams and 21-day-old male and female rats, perinatally exposed to MeHg (1 mg/kg/day, GD7-PND7) and PCB153 (20 mg/kg/day, GD10–GD16), alone or combined. Data are the mean ± SEM of n = 3–9 rats/treatment group/gender. *Significantly different from control group, P < 0.05.

Figure 2

Levels of (a) p-MAO-B activity (n = 137) and (b) l-MR binding measured in the blood of both female and male Faroese children. (a) illustrates the individual values of the MAO-B activity in 70 boys (mean ± SD = 6.08 ± 3.12 nmol/mg protein/h, range: 0.95–14.57) and 67 girls (mean ± SD = 5.56 ± 2.55 nmol/mg protein/h, range: 1.57–14.95), respectively. (b) shows the single values of the MR binding in 73 boys (mean ± SD = 8.05 ± 9.13 fmol/10⁶ cells, range: 0.1–36.78) and 66 girls (mean ± SD = 8.09 ± 8.31 fmol/10⁶ cells, range: 0.1–35.91), respectively.