Neurobehavioral changes and alteration of gene expression in the brains of metallothionein-I/II null mice exposed to low levels of mercury vapor during postnatal development.
This study examined the neurobehavioral changes and alteration in gene expression in the brains of metallothionein (MT)-I/II null mice exposed to low-levels of mercury vapor (Hg(0)) during postnatal development. MT-I/II null and wild-type mice were repeatedly exposed to Hg(0) at 0.030 mg/m(3) (range: 0.023-0.043 mg/m(3)), which was similar to the current threshold value (TLV), for 6 hr per day until the 20th day postpartum. The behavioral effects were evaluated with 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) at 12 weeks of age. Hg(0)-exposed MT-I/II null mice showed a significant decrease in total locomotor activity in females, though learning ability and spatial learning ability were not affected. Immediately after Hg(0) exposure, mercury concentrations in the brain did not exceed 0.5 µg/g in any animals. Hg(0) exposure resulted in significant alterations in gene expression in the brains of both strains using DNA microarray analysis. The number of altered genes in MT-I/II null mice was higher than that in wild-type mice and calcium-calmodulin kinase II (Camk2a) involved in learning and memory in down-regulated genes was detected. These results provide useful information to elucidate the development of behavioral toxicity following low-level exposure to Hg(0).
Faculty of Human Health Science, Hachinohe University, Hachinohe, Japan. m2yosida@hachinohe-u.ac.jp
Minoru
M
Yoshida
Masako
M
Honda
Chiho
C
Watanabe
Masahiko
M
Satoh
Akira
A
Yasutake
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008628:Mercury / Q000493:pharmacokinetics / Q000633:toxicity*; D020262:Mercury Poisoning, Nervous System / Q000235:genetics* / Q000503:physiopathology; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects; D014018:Tissue Distribution; D014835:Volatilization
D008668:Metallothionein; D008628:Mercury