Methylmercury (MeHg) is known to cause neurobehavioral impairment in human and experimental animals. We previously reported that MeHg (5 mg Hg/kg) induced severe neurobehavioral dysfunction in 4-week-old KK-Ay mice, although it is difficult to evaluate quantitatively the neurobehavioral impairment in MeHg-treated KK-Ay mice because of their obesity. The aim of this study was to evaluate MeHg-induced neurobehavioral dysfunction in KK-Ay mice using the dynamic weight-bearing test, which analyzes the animal's weight distribution between the four limbs. Male 12-week-old KK-Ay mice were treated with MeHg (5 mg Hg/kg) three times per week for 5 weeks. Body weight loss began after approximately 2 weeks of MeHg treatment, and decreased significantly at 4 weeks. Seven of the nine MeHg-treated mice exhibited overt neurological symptoms such as ataxia and gait disturbance. The weight-bearing load was lower for the forelimb than for the hindlimb at baseline and until 1 week after MeHg treatment was initiated. In weeks 2-4, the dynamic weight-bearing loads on the forelimb and hindlimb were similar. The load on the forelimb exceeded the load on the hindlimb after 5 weeks of treatment. This finding indicates that the dynamic weight-bearing test is useful for semi-quantitative evaluation of neurobehavioral impairment in MeHg-treated rodents, and is less stressful for the animals. Infiltration of CD204-positive macrophages was observed in the sciatic nerve of MeHg-treated mice, suggesting that CD204 can serve as a useful marker of tissue injury in peripheral nerves and a possible target in regenerating peripheral nerves and controlling neuropathies.
Keywords: CD204; diabetic mouse; dynamic weight-bearing test; macrophage; methylmercury; neurobehavioral impairment; peripheral nerve.
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Increased methylmercury toxicity related to obesity in diabetic KK-Ay mice.J Appl Toxicol. 2014 Aug;34(8):914-23. doi: 10.1002/jat.2954. Epub 2013 Nov 15. J Appl Toxicol. 2014. PMID: 24243536
Effects of perinatal coexposure to methylmercury and polychlorinated biphenyls on neurobehavioral development in mice.Arch Toxicol. 2008 Jun;82(6):387-97. doi: 10.1007/s00204-007-0254-x. Epub 2007 Nov 9. Arch Toxicol. 2008. PMID: 17992516
Neurobehavioral effects of combined prenatal exposure to low-level mercury vapor and methylmercury.J Toxicol Sci. 2011 Jan;36(1):73-80. doi: 10.2131/jts.36.73. J Toxicol Sci. 2011. PMID: 21297343
Neurobehavioral effects of developmental methylmercury exposure.Environ Health Perspect. 1995 Sep;103 Suppl 6(Suppl 6):135-42. doi: 10.1289/ehp.95103s6135. Environ Health Perspect. 1995. PMID: 8549462 Free PMC article. Review.
Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies.Life Sci. 2011 Oct 10;89(15-16):555-63. doi: 10.1016/j.lfs.2011.05.019. Epub 2011 Jun 13. Life Sci. 2011. PMID: 21683713 Free PMC article. Review.
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