Review about the manganese speciation project related to neurodegeneration: An analytical chemistry approach to increase the knowledge about manganese related parkinsonian symptoms

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• 作者：Bernhard Michalke ; ^{bernhard.michalke@helmholtz-muenchen.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AD ; Alzheimer disease ; CSF ; cerebrospinal fluid ; CE ; capillary electrophoresis ; CZE ; capillary zone electrophoresis ; DMT-1 ; divalent metal transporter 1 ; DRC ; dynamic reaction cell ; ESI-FT-ICR-MS ; electrospray ionization&mdash ; Fourier transform ion cyclotron resonance&mdash ; mass spectrometry ; Fe(S) ; total Fe in serum ; Fe-Tf(S) ; Fe-transferrin in serum ; Fe-Cit(S) ; Fe-citrate in serum ; GPx ; glutathione peroxidase ; IC ; ion chromatography ; ICP-MS ; inductively coupled plasma mass spectrometry ; ICP-OE
• 刊名：Journal of Trace Elements in Medicine and Biology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：37
• 期：Complete
• 页码：50-61
• 全文大小：3303 K

文摘

Neurodegenerative diseases get a growing relevance for societies. But yet the complex multi-factorial mechanisms of these diseases are not fully understood, although it is well accepted that metal ions may play a crucial role. Manganese (Mn) is a transition metal which has essential biochemical functions but from occupational exposure scenarios it appeared that Mn can cause severe neurological damage. This “two-faces”-nature of manganese initiated us to start a project on Mn-speciation, since different element species are known to exhibit different impacts on health. A summary about the step-wise developments and findings from our working group was presented during the annual conference of the German trace element society in 2015.

This paper summarizes now the contribution to this conference. It is intended to provide a complete picture of the so far evolved puzzle from our studies regarding manganese, manganese speciation and metabolomics as well as Mn-related mechanisms of neural damage. Doing so, the results of the single studies are now summarized in a connected way and thus their interrelationships are demonstrated. In short terms, we found that Mn-exposure leads to an increase of low molecular weight Mn compounds, above all Mn-citrate complex, which gets even enriched across neural barriers (NB). At a Mn serum concentration between 1.5 and 1.9 μg/L a carrier switch from Mn-transferrin to Mn-citrate was observed. We concluded that the Mn-citrate complex is that important Mn-carrier to NB which can be found also beyond NB in human cerebrospinal fluid (CSF) or brain of exposed rats. In brain of Mn-exposed rats manganese leads to a decreased iron (Fe) concentration, to a shift from Fe(III) to Fe(II) after long term exposure and thus to a shift toward oxidative stress. This was additionally supported by an increase of markers for oxidative stress, inflammation or lipid peroxidation at increased Mn concentration in brain extracts. Furthermore, glutamate and acetylcholineesterase were elevated and many metabolite concentrations were significantly changed.