Metal bashing: iron deficiency and manganese overexposure impact on peripheral nerves

ABSTRACT

Iron (Fe) deficiency (FeD) and manganese (Mn) overexposure (MnOE) may result in several neurological alterations in the nervous system. Iron deficiency produces unique neurological deficits due to its elemental role in central nervous system (CNS) development and myelination, which might persist after normalization of Fe in the diet. Conversely, MnOE is associated with diverse neurocognitive deficits. Despite these well-known neurotoxic effects on the CNS, the influence of FeD and MnOE on the peripheral nervous system (PNS) remains poorly understood. The aim of the present investigation was to examine the effects of developmental FeD and MnOE or their combination on the sciatic nerve of young and adult rats. The parameters measured included divalent metal transporter 1 (DMT1), transferrin receptor (TfR), myelin basic protein (MBP) and peripheral myelin protein 22 (PMP22) expression, as well as Fe levels in the nerve. Our results showed that FeD produced a significant reduction in MBP and PMP22 content at P29, which persisted at P60 after Fe-sufficient diet replenishment regardless of Mn exposure levels. At P60 MnOE significantly increased sciatic nerve Fe content and DMT1 expression. However, the combination of FeD and MnOE produced no marked motor skill impairment. Evidence indicates that FeD appears to hinder developmental peripheral myelination, while MnOE may directly alter Fe homeostasis. Further studies are required to elucidate the interplay between these pathological conditions.

KEYWORDS:

• Iron
• manganese
• peripheral nervous system
• myelination

Acknowledgments

The authors would like to thank Ms María Marta Rancez for her assistance in the elaboration of this manuscript.

Conflict of interest

Authors declare no conflict of interest.

Additional information

Funding

This work was supported by grants from Universidad de Buenos Aires (UBACYT 20020100101017) and CONICET (PIP 567) to PSA, National Institutes of Health (NIH) RO1 ES15689 to MTW, T32 ES007051 to CVV and P30 ES006096 to RMAK;Consejo Nacional de Investigaciones Científicas y Técnicas [PIP567];NIH [P30 ES006096,T32 ES007051];NIH [RO1 ES15689];