Evaluation of neurobehavioral impairment in methylmercury‐treated KK‐Ay mice by dynamic weight‐bearing test

• Published in: Journal of applied toxicology 2019-02, Vol.39 (2), p.221-230
• Main Authors: Yamamoto, Megumi, Motomura, Eriko, Yanagisawa, Rie, Hoang, Van Anh Thi, Mogi, Masaki, Mori, Tomohisa, Nakamura, Masaaki, Takeya, Motohiro, Eto, Komyo
• Format: Article
• Language: English
• Subjects: Animals; Ataxia; Body weight; Body weight loss; CD204; Diabetes; diabetic mouse; Dimethylmercury; dynamic weight‐bearing test; Evaluation; Gait; Impairment; Infiltration; Load; macrophage; Macrophages; Mercury; Mercury (metal); Methylmercury; Mice; Movement disorders; Nervous system; neurobehavioral impairment; peripheral nerve; Peripheral nerves; Peripheral neuropathy; Quantitative analysis; Rodents; Sciatic nerve; Weight loss
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.3710

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. The dynamic weight‐bearing test can detect changes in balance between the forelimb and hindlimb in methylmercury‐treated KK‐Ay type 2 diabetic mice, and is useful for semi‐quantitative evaluation of neurobehavioral impairment. Infiltration of CD204‐positive macrophages in the sciatic nerve of methylmercury‐treated mice indicated that CD204 could serve as a marker of tissue injury in peripheral nerves and a possible target in regenerating peripheral nerves and controlling neuropathies.