Effect of manganese treatment on the accumulation on biologically relevant metals in rat cochlea and brain by inductively coupled plasma mass spectrometry

Abstract

Manganese (Mn), iron (Fe), zinc (Zn), and copper (Cu) are essential transitions metals that are required in trace amounts, however chronic exposure to high concentrations can cause severe and irreversible neurotoxicity. Since prolonged exposure to Mn leads to manganism, a disorder exhibiting a diverse array of neurological impairments progressing to a debilitating and irreversible extrapyramidal condition symptomatically similar to Parkinson's disease, we measured the concentration of Mn as well as Fe, Zn and Cu in three region of the brain (globus pallidus, striatum and inferior colliculus) and three regions in the cochlea (stria vascularis, basilar membrane and modiolus) under normal conditions or after 30 or 60 days of oral administration of Mn (10 mg/ml ad libitum). Under normal conditions, Mn, Zn and Fe were typically higher in the cochlea than in the three brain regions whereas Cu was equal to or lower. Oral treatment with Mn for 30 or 60 days resulted in 20-75 % increases in Mn concentrations in both cochlea and brain samples, but had little effect on Cu and Fe levels. In contrast, Zn levels decreased (20-80 %) with Mn exposure. Our results show for the first time how prolonged oral Mn-ingestion affects the concentration of Mn, Cu, Zn and Fe, in the three regions of the cochlea, the inferior colliculus in auditory midbrain and the striatum and globus pallidus, two regions implicated in Parkinson's disorder. The Mn-induced changes in the concentration of Mn, Cu, Zn and Fe may provide new insights relevant to the neurotoxicity of Mn and the transport and accumulation of these metals in cochlea and brain.

The effect of high dose oral manganese exposure on copper, iron and zinc levels in rats

“…One of the affected tissues was frontal cortex, a region known to exhibit neuronal degeneration and other pathologies following in vivo Mn exposure in non-human primates (Guilarte et al 2008). Notably, oral Mn exposure in rats has recently been shown to influence Cu, Fe and Zn levels in other brain regions (Mullin et al 2015). Metal excess in frontal cortex after Mn exposure may have implications for the interpretation of magnetic resonance imaging (MRI) findings following Mn exposure.…”