Perinatal and Lifetime Exposure to Methylmercury in the Mouse: Behavioral Effects

This project was undertaken to more completely understand the consequences of lifetime exposure to methylmercury. A series of experiments examined how perinatal or lifetime exposure to methylmercury affected behavioral performances in the adult mouse at different ages. One hundred female B6C3F1/HSD mice were assigned to one of three dose groups, 0 ppm, 1 ppm, or 3 ppm methylmercury chloride administered in a 5 nM sodium carbonate drinking solution. Four weeks after initiating dosing, the females were bred with male CBA/J HSD mice to produce the trihybrid offspring B6C3F1/HSD × CBA/J HSD. The methylmercury-treated litters were split into two subgroups, one exposed throughout its lifetime to the original dose, the other exposed through postnatal day 13. Altogether, then, five groups were studied: Control, 1 ppm perinatal, 1 ppm lifetime, 3 ppm perinatal, and 3 ppm lifetime. Three neurobehavioral indices were evaluated: (1) delayed spatial alternation (a test of memory) and (2) running in a wheel to earn food pellets (schedule-controlled operant behavior) were assessed starting at 5 and 15 months of age; (3) hindlimb splay, a measure of motor function, was assessed at 5, 15, and 26 months of age. Subjects tested at one age were littermates of those tested at the other ages. MeHg altered the hindlimb splay distance; control mice differed from methylmercury-exposed mice, the 1 ppm lifetime and 3 ppm lifetime groups differed from each other, and the analysis yielded an age by dose interaction. MeHg exposure altered different measures of wheel running under the 3 ppm lifetime condition. In the delayed alternation procedure, the mouse was required to respond to one of two locations in a strictly alternating sequence. More mice from the treated groups, except for the 1 ppm perinatal group, failed to meet the criterion at longer delay values. Overall, the results show that exposure to low levels of methylmercury produces behavioral effects that depend on the test procedure, the dose, the duration of exposure, and the age. Lifetime evaluations of exposure to toxicants, beginning with early development, should be a component of the risk assessment process for neurotoxicity.