Manganese neurotoxicity: new perspectives from behavioral, neuroimaging, and neuropathological studies in humans and non-human primates

Abstract

Manganese (Mn) is an essential metal and has important physiological functions for human health. However, exposure to excess levels of Mn in occupational settings or from environmental sources has been associated with a neurological syndrome comprising cognitive deficits, neuropsychological abnormalities and parkinsonism. Historically, studies on the effects of Mn in humans and experimental animals have been concerned with effects on the basal ganglia and the dopaminergic system as it relates to movement abnormalities. However, emerging studies are beginning to provide significant evidence of Mn effects on cortical structures and cognitive function at lower levels than previously recognized. This review advances new knowledge of putative mechanisms by which exposure to excess levels of Mn alters neurobiological systems and produces neurological deficits not only in the basal ganglia but also in the cerebral cortex. The emerging evidence suggests that working memory is significantly affected by chronic Mn exposure and this may be mediated by alterations in brain structures associated with the working memory network including the caudate nucleus in the striatum, frontal cortex and parietal cortex. Dysregulation of the dopaminergic system may play an important role in both the movement abnormalities as well as the neuropsychiatric and cognitive function deficits that have been described in humans and non-human primates exposed to Mn.

Developmental exposure to manganese induces lasting motor and cognitive impairment in rats

“…Non-motor symptoms have also been associated with excessive Mn exposure (Guilarte et al, 2008b;Aschner et al, 2009;Guilarte, 2013). Neuropathological changes in frontal cortex of non-human primates as a consequence of Mn exposure have also been described (Verina et al, 2013).…”

Cognitive Effects of Manganese in Children and Adults

“…Emerging evidence of the cognitive effects of Mn has focused attention on brain regions such as the frontal cortex, and other cortical and subcortical structures related to the cognitive domains. 28 …”

Manganese and Parenteral Nutrition

“…The pallidal index explained approximately 20-30% of the variance in standardized test scores in this study, while blood Mn rarely exceeds 20%. 106 While the pallidal index is still the best-studied marker of Mn accumulation, recent studies point to the frontal cortex 107,108 and the hippocampus and thalamus 109,110 as structures also evidencing Mn deposition. More global Mn deposition, including in the frontal cortex, would reduce the sensitivity of the pallidal index.…”