Neurobehavioral changes in response to alterations in gene expression profiles in the brains of mice exposed to low and high levels of mercury vapor during postnatal development

• Published in: Journal of toxicological sciences Vol. 39; no. 4; pp. 561 - 570
• Main Authors: Yoshida, Minoru, Honda, Akiko, Watanabe, Chiho, Satoh, Masahiko, Yasutake, Akira
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 01.08.2014; Japan Science and Technology Agency
• Subjects: Animals; Animals, Newborn; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Brain - metabolism; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Female; Gene expression; Gene Expression - drug effects; Learning - drug effects; Male; Maze Learning - drug effects; Mercury Compounds - metabolism; Mercury Compounds - toxicity; Mercury vapor; Mice, Inbred C57BL; Microarray; Motor Activity - drug effects; Neonatal exposure; Neurobehavioral effects; Spatial Navigation - drug effects; Tissue Distribution; Up-Regulation - drug effects; Volatilization
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.39.561

This study examined the relationship between neurobehavioral changes and alterations in gene expression profiles in the brains of mice exposed to different levels of Hg0 during postnatal development. Neonatal mice were repeatedly exposed to mercury vapor (Hg0) at a concentration of 0.057 mg/m3 (low level), which was close to the current threshold value (TLV), and 0.197 mg/m3 (high level) for 24 hr until the 20th day postpartum. Behavioral responses were evaluated based on changes in locomotor activity in the open field test (OPF), learning ability in the passive avoidance response test (PA), and spatial learning ability in the Morris water maze (MM) at 12 weeks of age. No significant differences were observed in the three behavioral measurements between mice exposed to the low level of Hg0 and control mice. On the other hand, total locomotive activity in mice exposed to the high level of Hg0 was significantly decreased and central locomotion was reduced in the OPF task. Mercury concentrations were approximately 0.4 μg/g and 1.9 μg/g in the brains of mice exposed to the low and high levels of Hg0, respectively. Genomic analysis revealed that the expression of 2 genes was up-regulated and 18 genes was down-regulated in the low-level exposure group, while the expression of 3 genes was up-regulated and 70 genes was down-regulated in the high-level exposure group. Similar alterations in the expression of seven genes, six down-regulated genes and one up-regulated gene, were observed in both groups. The results indicate that an increase in the number of altered genes in the brain may be involved in the emergence of neurobehavioral effects, which may be associated with the concentration of mercury in the brain. Moreover, some of the commonly altered genes following exposure to both concentrations of Hg0 with and without neurobehavioral effects may be candidates as sensitive biomarker genes for assessing behavioral effects in the early stages of development.