Abstract
Exposure to high concentrations of Manganese (Mn) is known to potentially induce an accumulation in the brain, leading to a Parkinson related disease, called manganism. Versatile mechanisms of Mn-induced brain injury are discussed, with inactivation of mitochondrial defense against oxidative stress being a major one. So far, studies indicate that the main Mn-species entering the brain are low molecular mass (LMM) compounds such as Mn-citrate. Applying a single low dose MnCl2 injection in rats, we observed alterations in Mn-species pattern within the brain by analysis of aqueous brain extracts by size-exclusion chromatography—inductively coupled plasma mass spectrometry (SEC-ICP-MS). Additionally, electrospray ionization—ion cyclotron resonance-Fourier transform-mass spectrometry (ESI-ICR/FT-MS) measurement of methanolic brain extracts revealed a comprehensive analysis of changes in brain metabolisms after the single MnCl2 injection. Major alterations were observed for amino acid, fatty acid, glutathione, glucose and purine/pyrimidine metabolism. The power of this metabolomic approach is the broad and detailed overview of affected brain metabolisms. We also correlated results from the metallomic investigations (Mn concentrations and Mn-species in brain) with the findings from metabolomics. This strategy might help to unravel the role of different Mn-species during Mn-induced alterations in brain metabolism.
Highlights
Manganese (Mn) is an essential trace element needed for proper functionality of various physiological processes, but can be very harmful to the body
We studied Mn-speciation in brain by hyphenation of a separation technique to a sensitive elemental detector ICP-MS, referring to the previous study by Diederich et al Since Mn-species naturally are very labile, size exclusion chromatography (SEC) of aqueous brain extracts was chosen as separation technique
Brains were taken for the determination of Mn concentrations and for an aqueous brain extraction applied for Mn-speciation
Summary
Manganese (Mn) is an essential trace element needed for proper functionality of various physiological processes, but can be very harmful to the body. When Mn is taken up in higher concentrations than recommended, it is transported into the brain via the bloodstream, where it can accumulate in the region of basal ganglia affecting dopaminergic nigrostriatal. Manganese and Brain Metallome/Metabolome the authors’ adherence to PLOS ONE policies on sharing data and materials. This results in a disease called manganism showing similarities to Parkinsons Disease (PD) due to the overlap in affected brain areas [2]. The role of Mn in the development of PD has been discussed [3]
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