Behavioral changes in metallothionein-null mice after the cessation of long-term, low-level exposure to mercury vapor.

The neurobehavioral changes in wild-type and metallothionein (MT)-null mice after the cessation of long-term, low-level exposure to Hg0 were investigated. MT-null and wild-type females were continuously (24 h/day) exposed to mercury vapor (Hg0) at 0.055 mg/m3 (range: 0.043-0.073 mg/m3), which was similar to the current threshold limit value (TLV), for 29 weeks. The effects on behavior, such as locomotor activity in the open field (OPF), learning ability in the passive avoidance response (PA) and spatial learning ability in the Morris water maze (MM) were examined immediately and 12 weeks after the cessation of exposure. Immediately after the exposure had ceased, total locomotor activity in OPF was decreased in the both strain of mice, although the MT-null mice appeared to show more distinct effect. In the PA test, the exposed animals of both strains showed learning impairment as compared to un-exposed mice. Twelve weeks after the cessation of exposure, the locomotor activity in OPF was elevated in the exposed mice of both strains, while the learning ability in the PA test appeared normal in both strains. Spatial learning ability was not affected at all. Immediately after the exposure had ceased, the brain mercury concentration of the exposed wild-type mice was 1.75 microg/g, twofold of that in the MT-null mice. In 12 weeks, brain mercury levels decreased to approximately 1/20 of those in immediately after the exposure in both of the strains. These results for the first time indicated that long-term, low-level exposure to Hg0 could exert neurobehavioral effects, which were not reversible even after a long exposure-free period. Whereas the effects on learning ability were presumably transient, the effects on spontaneous behavior as evaluated in OPF were persistent. Finally, the MT-null mice seemed more susceptible to Hg0-induced neurotoxicity than the wild-type mice, confirming our previous results.