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

TLDR

Manganese is essential for health but excess exposure in occupational or environmental settings causes neurological deficits, historically linked to basal ganglia dysfunction, with emerging evidence of cortical and cognitive effects at lower levels. The review aims to elucidate mechanisms by which excess manganese disrupts neurobiological systems, leading to deficits in both basal ganglia and cerebral cortex. It examines putative mechanisms of manganese‑induced neurobiological disruption affecting both basal ganglia and cortical structures. Evidence shows chronic manganese exposure impairs working memory through changes in caudate, frontal, and parietal regions, and dopaminergic dysregulation underlies movement, neuropsychiatric, and cognitive deficits in humans and 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.