Manganese-induced Parkinsonism in mice is reduced using a novel contaminated water sediment exposure model

Abstract

<jats:title>Abstract</jats:title><jats:p>The effects of heavy metals on human health have become an important area of study. For instance, acute manganese toxicity is known to induce Parkinsonism. Heavy metals including manganese enter the aquatic environment from both anthropogenic and natural processes. These metals accumulate within water sediments and their behavior is then dependent upon the sediment composition and phase. These metal-sediment interactions remain to be explored within <jats:italic>in-vivo</jats:italic> animal studies. To study the effect of these interactions, herein we successfully developed an exposure model in mice that encapsulates the aquatic microenvironment of heavy metals before exposure. Male and female <jats:italic>C57/BL6</jats:italic> mice were exposed to manganese contaminated sediment via their drinking water (Sed_Mn) or to manganese placed directly into their drinking water with no prior sediment interaction (Mn) for six weeks. Sediment interaction did not alter total manganese in drinking water (mg/L) or weekly manganese consumption (mg) in males (54.9±1.5 mg) or females (44.6±1.0 mg) over the six-week exposure period. We analyzed motor impairment, a common feature in Parkinson’s disease, using the beam traversal, cylinder, and accelerating rotarod behavioral tests. We observed Parkinson’s like deficits in motor control in both treatment groups as early as four weeks of exposure in males but not in females. Intriguingly, mice given water incubated with manganese spiked sediment (Sed_Mn) performed better overall compared to mice given manganese directly in water (Mn) despite having similar exposure in males and females. Male Sed_Mn mice compared to Mn mice had a 146% reduction in time to cross the beam traversal test (<jats:italic>p&lt;0.05</jats:italic>), a 10% increase in rearing activity in the cylinder test (<jats:italic>p&lt;0.05</jats:italic>), and a 14% increase in time remaining on the rotarod (<jats:italic>not significant</jats:italic>). Female Sed_Mn mice compared to Mn mice had no change in the time to cross the beam traversal test, a 36% increase in rearing activity in the cylinder test (<jats:italic>p&lt;0.05</jats:italic>), and a 35% increase in time on the rotarod (<jats:italic>p&lt;0.05</jats:italic>). Our study indicates that metal-sediment interactions may alter metal toxicity in mammals and introduces a new exposure model to test the toxicity of metal contaminants of drinking water.</jats:p>