Kim et al. 2026 — Mixed Pb/MeHg/Cd exposure and hippocampal dopamine in mice
Fifty male ICR mice were divided into five groups and exposed for 28 days via drinking water to lead (25 mg/L as lead acetate), methylmercury (10 mg/L as methylmercury chloride), cadmium (15 mg/L as cadmium chloride), or all three combined; spatial memory was assessed by the Morris water maze and dopaminergic markers were quantified in hippocampal tissue. The combined-exposure group showed significantly greater spatial memory deficits than any single-metal group, and hippocampal dopamine levels were substantially lower in the combined group, indicating synergistic rather than additive neurotoxicity. Dopaminergic pathway proteins — tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine receptors D1 and D2 (DRD1, DRD2) — were all downregulated in the combined group relative to single-metal groups, suggesting convergent disruption of dopamine synthesis, reuptake, and signaling. The study is relevant to the heavy metals-in-food domain because Pb, MeHg, and Cd are the three food-route metals with the highest dietary exposure for vulnerable human populations, and co-exposure is the rule rather than the exception.
Key numbers
- Exposure concentrations: Pb 25 mg/L, MeHg 10 mg/L, Cd 15 mg/L in drinking water, 28-day exposure
- Groups: control (n=10), Pb alone (n=10), MeHg alone (n=10), Cd alone (n=10), combined (n=10)
- Spatial memory (Morris water maze escape latency, day 5): combined group significantly higher than all single-metal groups (exact ms values in source tables)
- Hippocampal dopamine: significantly reduced in combined group vs single-metal groups (exact values in source figures)
- Dopaminergic markers (TH, DAT, DRD1, DRD2): all significantly lower in combined vs single-metal groups by western blot and RT-qPCR
- Institution: Keimyung University, Daegu, Republic of Korea
Methods (brief)
Male ICR mice, 28-day oral exposure via drinking water at concentrations mimicking subchronic human occupational/environmental scenarios. Morris water maze for spatial memory (5-day acquisition, 1-day probe trial). Hippocampal tissue dissected post-sacrifice. Dopamine quantified by HPLC-ECD. Protein expression by western blot; gene expression by RT-qPCR. Statistical analysis by one-way ANOVA with Tukey post-hoc. No speciation of mercury confirmed independently; exposure was methylmercury chloride by design.
Implications
Certification: Provides mechanistic support for the biological rationale behind multi-metal food safety standards; the synergistic neurotoxicity finding supports treating co-exposure — not just individual metals — as the relevant exposure scenario for infants consuming multiple metal-containing food matrices. Relevant to HMT&C’s multi-analyte testing approach.
Courses: Core content for the neurotoxicity module. Illustrates that assessing metals individually understates risk when co-exposure is likely; relevant to infant formula, baby food, and fish consumption contexts.
App: Does not contribute concentration data; informs the exposure-risk framing for multi-metal co-exposure scenarios. The app should treat simultaneous high readings for Pb + MeHg + Cd in a product as a compound risk signal, not as three independent risks.