ToxSci Advance Access published online on April 7, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh138
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Biochemistry, Division of Chemistry, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 261-8511, Japan
* To whom correspondence should be addressed. E-mail: chiho{at}humeco.m.u-tokyo.ac.jp.
While recent human studies suggested adverse neurobehavioral outcomes of low-level exposure to the mercury vapour (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 metallothioein-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 wk 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 the brain Hg concentration less than 1 ppm. These effects were slightly exaggerated in MT-null mice, which showed less induction of MT, had lower brain Hg concentration, and lower calculated concentration of MT-unbound cytosolic Hg. The results for the first time showed that the 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 non-kinetic mechanisms.
© 2004 Toxicological Sciences © Society of Toxicology 2004; all rights reserved.
Neurotoxicology
Susceptibility of Metallothionein-Null Mice to the Behavioural Alterations Caused by Exposure to Mercury Vapour at Human-Relevant Concentration
2 Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
3 Department of Hygienics, Gifu Pharmaceutical University, 5-6-1, Mitahora-higashi, Gifu 502-8585, Japan
4 Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008, Japan
5 Department of Veterinary Pathology, Tottori University, Minami 4-101, Tottori-shi, Tottori 680-0945, Japan
6 Department of Chemistry, Meisei University, Hino, Tokyo 191-0041 Japan
7 Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-0053, Japan
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Aschner, T. Syversen, D. O. Souza, and J. B.T. Rocha Metallothioneins: mercury species-specific induction and their potential role in attenuating neurotoxicity. Experimental Biology and Medicine, October 1, 2006; 231(9): 1468 - 1473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Stacchiotti, F. Ricci, R. Rezzani, G. Li Volti, E. Borsani, A. Lavazza, R. Bianchi, and L. F. Rodella Tubular Stress Proteins and Nitric Oxide Synthase Expression in Rat Kidney Exposed to Mercuric Chloride and Melatonin J. Histochem. Cytochem., October 1, 2006; 54(10): 1149 - 1157. [Abstract] [Full Text] [PDF]
|
|