Emergence of Delayed Methylmercury Toxicity after Perinatal Exposure in Metallothionein-Null and Wild-Type C57BL Mice
- 1 June 2008
- journal article
- Published by Environmental Health Perspectives in Environmental Health Perspectives
- Vol. 116 (6), 746-751
- https://doi.org/10.1289/ehp.10906
Abstract
Although a long latency period of toxicity after exposure to methylmercury (MeHg) is known to exist in humans, few animal studies have addressed this issue. Substantiation of delayed MeHg toxicity in animals would affect the risk evaluation of MeHg. Our goal in this study was to demonstrate the existence of a latency period in a rodent model in which the toxicity of perinatal MeHg exposure becomes apparent only later in life. Our study included metallothionein (MT) knockout mice because studies have suggested the potential susceptibility of this strain to the neurodevelopmental toxicity of MeHg. Pregnant MT-null and wild-type C57Bl/6J mice were exposed to MeHg through their diet containing 5 μg Hg/g during gestation and early lactation. We examined behavioral functions of the offspring using frequently used paradigms, including open field behavior (OPF), passive avoidance (PA), and the Morris water maze (MM), at ages of 12–13 and 52–53 weeks. At 12 weeks of age, behavioral effects of MeHg were not detected, except for OPF performance in MeHg-exposed MT-null females. At 52 weeks of age, the MeHg-exposed groups showed poorer performance both in PA and MM, and their OPF activity differed from controls. These effects of MeHg appeared exaggerated in the MT-null strain. The brain Hg concentration had leveled off by 13 weeks of age. The results suggest the existence of a long latency period after perinatal exposure to low-level MeHg, in which the behavioral effects emerged long after the leveling-off of brain Hg levels. Hence, the initial toxicologic event responsible for the late effects should have occurred before this leveling-off of brain Hg.Keywords
This publication has 41 references indexed in Scilit:
- Diet-Induced Obesity in Female Mice Leads to Offspring Hyperphagia, Adiposity, Hypertension, and Insulin ResistanceHypertension, 2008
- Maintaining Equilibrium by Selective Targeting of Cyclooxygenase PathwaysHypertension, 2008
- Metallothionein I and II Attenuate the Thalamic Microglial Response following Traumatic Axotomy in the Immature BrainJournal of Neurotrauma, 2007
- Effects of perinatal exposure to low doses of cadmium or methylmercury on thyroid hormone metabolism in metallothionein-deficient mouse neonatesToxicology, 2006
- Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 yearsNeurotoxicology and Teratology, 2006
- Behavioral changes in metallothionein-null mice after the cessation of long-term, low-level exposure to mercury vaporToxicology Letters, 2006
- Age-dependent measures of anxiety and cognition in male histidine decarboxylase knockout (Hdc−/−) miceBrain Research, 2006
- Susceptibility of Metallothionein-Null Mice to the Behavioral Alterations Caused by Exposure to Mercury Vapor at Human-Relevant ConcentrationToxicological Sciences, 2004
- Selective quantification of inorganic mercury in tissues of methylmercury-treated ratsBulletin of Environmental Contamination and Toxicology, 1990
- Sex and age differences in mercury distribution and excretion in methylmercury‐administered miceJournal of Toxicology and Environmental Health, 1986