Explorating the mechanism of Mn-induced dopaminergic injury

Abstract

Manganese (Mn) is an essential trace element contributingto various physiological processes like brain development,diverse metabolisms and proper function of antioxidativeenzymes like Acetylcholinesterase (AchE) (Erikson et al.,2005). On the downside, overexposure to Mn can lead to thedegeneration of dopaminergic neurons inducing a Parkinson-like complaint called manganism. Extensive studies havebeen carried out to decipher transport routes into thebrain and to detect cellular mechanisms of oxidative injuryin the affected brain areas (Crossgrove et al., 2003; Yokel,2009 ;Yokel and Crossgrove, 2004 Aschner et al., 2007).Nevertheless, the correlation between the active Mn-species and the occurring conceivable causes of oxidativeinjury has not been drawn so far. The aim of this study istherefore, to elucidate the predominant Mn-species in theexposed brain and link it to levels of glutamate or GABA,AchE activity, Fe(II)/(III) status and levels of other traceelements like Cu, Fe or Zn (Figure 1).The applied model was a feeding trial of rats, where Mnlevels were elevated (500 mg/kg) in a non-toxic manner inthe test group and which lasted for 53 days.After removal of the brain, it was deep frozen androughly homogenized. Levels of Mn, Cu, Fe and Zn weredetermined in the whole brain by ICP-OES or –MS. Mn levelswere significantly higher in Mn-exposed (test) rats comparedto normal exposed (control) rats, which was interestinglyalso true for Cu levels. Furthermore an aqueous extractionof the brain served as matrix for determination of AchEactivity as well as glutamate and GABA levels by commercialavailable kits. Test rats showed significantly elevated AchEactivity as well as increased glutamate levels, indicatingoxidative stress in the affected brain tissue (Erikson andAschner, 2003; Melo et al., 2003). The same brain extractswere applied for determination of the Fe(II)/(III) status by