Effect of Hfe Deficiency on Memory Capacity and Motor Coordination after Manganese Exposure by Drinking Water in Mice

Toxicological Research
Helal Hussain AlsulimaniJonghan Kim

Abstract

Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout (Hfe (-/-)) and their control wild-type (Hfe (+/+)) mice to MnCl2 in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed tha...Continue Reading

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Dec 18, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jonghan KimMarianne Wessling-Resnick
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May 25, 2013·PloS One·Jonghan KimMarianne Wessling-Resnick
Aug 27, 2014·The Journal of Nutritional Biochemistry·Jonghan Kim, Marianne Wessling-Resnick
May 20, 2015·Journal of Neurochemistry·Pan ChenMichael Aschner

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Citations

Nov 10, 2015·Toxicology·Archita Venugopal MenonJonghan Kim
Jul 13, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thibault CaveyOlivier Loréal
Jun 18, 2017·Metallomics : Integrated Biometal Science·Qi YeJonghan Kim
May 20, 2016·The Journal of Toxicological Sciences·Devina SaputraKyuhong Lee

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