Elsevier

NeuroToxicology

Volume 41, March 2014, Pages 141-142
NeuroToxicology

Brief communication
Considerations on manganese (Mn) treatments for in vitro studies

https://doi.org/10.1016/j.neuro.2014.01.010Get rights and content

Highlights

  • We perform calculations to evaluate relevant in vitro exposures to Mn.

  • We establish media levels of Mn in the range of 60.1–158.4 μM are relevant to testing its toxicity.

Abstract

Manganese (Mn) is an environmental risk factor for neuronal dysfunction and neurodegeneration of the basal ganglia and other brain regions. Aberrant brain Mn levels have been linked to manganism, Parkinson's disease (PD), Huntington's disease (HD) and other neurological disorders. Research on the cellular basis of Mn neurotoxicity has relied upon in vitro or non-human model systems. However, an analysis of relevant Mn concentrations for in vitro studies is lacking – and few studies have examined intracellular Mn levels. Here we perform calculations to evaluate in vitro exposure paradigms in relation to relevant in vivo levels of Mn post-exposure.

Introduction

Exposure to high manganese (Mn) levels in occupational or environmental settings or disease conditions is accompanied by Mn accumulation in brain regions highly sensitive to oxidative injury, namely the substantia nigra (SN), globus pallidus (GP) and striatum (Newland et al., 1989, Cersosimo and Koller, 2006, Olanow, 2004, Guilarte, 2010). Excessive Mn deposition in these regions leads to dopaminergic (DAergic) neuronal loss accompanied by an extrapyramidal syndrome referred to as manganism. Manganism patients exhibit rigidity, tremor, dystonic movements and bradykinesia, all characteristic features of Parkinson's disease (PD) (Cersosimo and Koller, 2006, Olanow, 2004, Guilarte, 2010, Calne et al., 1994). Exposure to Mn also represents a risk factor for PD (Gorell and Peterson, 2004). Indeed, one of the strongest correlations between environmental exposure and PD is noted in Mn-exposed human cohorts (Hudnell, 1999). Parkinsonism in welders (vs. non-welders) is clinically distinguishable only by age of onset (46 vs. 63 years, respectively) and the prevalence of PD is higher among welders compared with age-standardized individuals in the general population (Criswell et al., 2011, Racette et al., 2005). Alterations in neuronal handling of Mn have also been observed in the context of Huntington's disease (Williams et al., 2010, Madison et al., 2012). Although a myriad of studies examined the cellular effects of Mn, surprisingly few have measured intracellular Mn concentrations. To assist the reader in determining relevant Mn concentrations for in vitro studies we provide the following calculations.

Section snippets

Results and discussion

Protein content in cultured astrocytes is 0.006409 mg/million cells (unpublished data). Assuming an average cell radius of 2.25 μm, crystalline protein s = ∼0.65 (Matthews, 1974), and volume (((4pi) × 3) × (radius cubed) × s) of 31.01 × 10−9 μl, we derive a protein content of 0.2067 mg/μl. Normal human brain Mn concentrations are in the range 1.1–2.9 ppm (Császma et al., 2003). These estimates may vary by a factor of 2 or more, dependent upon cell size and the established propensity of astrocytes to more

Conflict of interest statement

None.

Acknowledgements

ABB and MA were supported in part by NIH grants, National Institute of Environmental Health Sciences R01 ES10563 (ABB and MA), ES016931 (ABB and MA), and the Molecular Toxicology Center P30 ES000267 (MA).

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References (16)

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