Methylmercury and nutrition: Adult effects of fetal exposure in experimental models

Human exposure to the life-span developmental neurotoxicant, methylmercury (MeHg), is primarily via the consumption of fish or marine mammals. Fish are also excellent sources of important nutrients, including selenium and n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA). Laboratory models of developmental MeHg exposure can be employed to assess the roles of nutrients and MeHg and to identify potential mechanisms of action if the appropriate exposure measures are used. When maternal exposure is protracted, relationships between daily intake and brain mercury are consistent and orderly across species, even when large differences in blood:brain ratios exist. It is well established that low-level developmental MeHg produces sensory deficits. Recent studies also show that perseveration in reversal-learning tasks occurs after gestational exposures that produce low micromolar concentrations in the brain. A no-effect level has not been identified for this effect. These exposures do not affect the acquisition or performance of discrimination learning, set shifting (extradimensional shift), or memory. Reversal-learning deficits may be related to enhanced impact of reinforcers as measured using progressive ratio reinforcement schedules, an effect that could result in perseveration. Also reported is enhanced sensitivity to dopamine reuptake inhibitors and diminished sensitivity to pentobarbital, a GABA(A) agonist. Diets rich in PUFAs or selenium do not protect against MeHg's effects on reversal learning but, by themselves, may diminish variability in performance, enhance attention or psychomotor function and may confer some protection against age-related deficits in these areas. It is hypothesized that altered reward processing, dopamine and GABAergic neurotransmitter systems, and cortical regions associated with choice and perseveration are especially sensitive to developmental MeHg at low exposure levels. Human testing for MeHg's neurotoxicity should emphasize these behavioral domains. (C) 2008 Elsevier Inc. All rights reserved.