Susceptibility of metallothionein-null mice to the behavioral alterations caused by exposure to mercury vapor at human-relevant concentration.
While recent human studies suggested adverse neurobehavioral outcomes of low-level exposure to mercury vapor (Hg0) as found among those having dental amalgam fillings and dental personnel, past animal experiments only dealt with exposure at much higher mercury concentrations. The present study aimed to examine neurobehavioral effects of prolonged, low-level Hg0 exposure in mice and to evaluate the protective role of metallothionein-I,II (MT-I,II) against Hg0-induced neurotoxicity, using a knock-out strain of mice. Adult female metallothionein-I,II-null (MT-null) and wild-type OLA129/C57BL6 mice were exposed to 0.06 mg/m3 of Hg0 for 8 h per day for 23 weeks. Neurobehavioral effects were evaluated at 12 and 23 weeks of exposure using open-field test and passive avoidance test. Subcellular distribution of mercury and the induction of MT were also assessed. The Hg0 exposure resulted in significantly enhanced locomotion in the open-field test and poorer performance in the passive avoidance test at a brain Hg concentration less than 1 ppm. These effects were slightly exaggerated in MT-null mice, which showed less induction of MT, lower brain Hg concentration, and lower calculated concentration of MT-unbound cytosolic Hg. The results showed, for the first time, that a concentration of Hg0 relevant to human exposure level could cause neurobehavioral effects in adult mice. The higher susceptibility of MT-null mice suggested that MT-I,II have protective roles in the metal-induced neurobehavioral toxicity, which cannot be entirely explained by kinetic mechanisms, thus suggesting an involvement of nonkinetic mechanisms.
Yoshida
Minoru
M
Department of Biochemistry, Division of Chemistry, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 261-8511, Japan.
Watanabe
Chiho
C
Satoh
Masahiko
M
Yasutake
Akira
A
Sawada
Masumi
M
Ohtsuka
Yuko
Y
Akama
Yoshifumi
Y
Tohyama
Chiharu
C
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007858:Learning / Q000187:drug effects; D008628:Mercury / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D020262:Mercury Poisoning, Nervous System / Q000235:genetics; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects
D000393:Air Pollutants; D008668:Metallothionein; D008628:Mercury