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

Abstract

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. In describing chronic exposures, 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 (extra-dimensional 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 GABAA 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.

Sex-dependent and non-monotonic enhancement and unmasking of methylmercury neurotoxicity by prenatal stress

“…Increases in brain Hg, but not in blood, were not proportional to increasing MeHg dose: ratios of total brain Hg levels at 2.5ppm relative to those at 0.5ppm averaged between 6.04–7.26 as compared to the 5-fold difference in nominal exposure concentrations (p<0.05), finding consistent with those reported by Newland et al (Newland et al, 2008). No interactions with either sex or stress were found, so blood and brain Hg levels increased equivalently in males and females and in NS and PS treated rats.…”

A hypothesis about how early developmental methylmercury exposure disrupts behavior in adulthood

“…These investigations are important but they are necessarily correlational, and therefore contain the confounding variables and ambiguities about causality embedded in epidemiological studies. To tease out cause-effect relations, our laboratory has directly compared the benefits of fish nutrients selenium (Se) and docosahexaenoic acid (DHA) under controlled experimental conditions using prenatal and adult-onset MeHg exposure (Newland and Paletz, 2000; Newland et al, 2008). …”

“…In contrast, maternal exposure for only three weeks of gestation to 0.5 ppm produced subtle but irreversible effects in the adult and aging offspring, even though by all cage-side observations these animals appeared perfectly healthy. That is, exposed animals showed no neurological signs, weight loss, reproductive toxicity, or changes in physical appearance even as they showed significant, if subtle, neurotoxicity as adults (Newland, 2012; Newland et al, 2008). Such sensitivity has been reported with auditory, visual, and somatosensory deficits in monkeys (Rice, 1996) and in behavioral studies with rodents (Bourdineaud et al, 2008; Bourdineaud et al, 2011; Castoldi et al, 2008; Liang et al, 2009; Montgomery et al, 2008; Newland et al, 2008; Onishchenko et al, 2008; Weiss et al, 2005) and are linked to disturbances in the development of the dopamine systems (Rasmussen and Newland, 2001; Reed and Newland, 2009).…”

Methyl Mercury Exposure through Seafood Diet and Its Effect on Aquatic Life and Health in United Arab Emirates

“…It is then transferred through the aquatic food chain to and eventually to humans through consumption (Meyers, 1998;Wooltron, 2002). central nervous system (Castoldi et al, 2008;Newland, Paletz, & Reed, 2008). However, mercury is present in almost every food and it is difficult for humans to survive only on food that do not contain mercury.…”