Manganese and Parkinson's disease: a critical review and new findings

Abstract

The goal of this review was to examine whether chronic Mn exposure produces dopamine neuron degeneration and PD or whether it has a distinct neuropathology and clinical presentation. I reviewed available clinical, neuroimaging, and neuropathological studies in humans and nonhuman primates exposed to Mn or other human conditions that result in elevated brain Mn concentrations. Human and nonhuman primate literature was examined to compare clinical, neuroimaging, and neuropathological changes associated with Mn-induced parkinsonism. Clinical, neuroimaging, and neuropathological evidence was used to examine whether Mn-induced parkinsonism involves degeneration of the nigrostriatal dopaminergic system as is the case in PD. The overwhelming evidence shows that Mn-induced parkinsonism does not involve degeneration of midbrain dopamine neurons and that l-dopa is not an effective therapy. New evidence is presented on a putative mechanism by which Mn may produce movement abnormalities. Confirmation of this hypothesis in humans is essential to make rational decisions about treatment, devise effective therapeutic strategies, and set regulatory guidelines.

Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism

“…However, PPL2ab DAergic neuronal cluster was the most affected by the three metals either in acute or chronic exposure but PPL3 was completely destroyed in chronic exposure by Cu and Mn. These data is in agreement with the notion that environmental toxins and metals may indiscriminately diminished DAergic neuron clusters in the fly's (Coulom and Birman 2004;Chaudhuri et al 2007) and human brain (Meenakshi-Sundaram et al 2008;Guilarte 2010). However, metals and xenotoxins were able to completely destroy DAergic neuronal clusters such as PPL3 (this work) and PPM3 by ROT (Coulom and Birman 2004) in the fly.…”

“…Moreover, we found that the reduction in life span and mobility abilities were related to abnormal accumulation of these metals in the fly's head. Taken together these observations imply that D. melanogaster is unable to effectively manage metal excess as it is found in impaired metal homeostasis in PD and Parkinsonism (Lee and Andersen 2010;Guilarte 2010;Huster 2010). Moreover, our data and others suggest that metal induced PD-like neurological dysfunction independently of the metal exposure route in vivo models [e.g.…”

“…However, homeostatic dysregulation might lead to metabolic (e.g., hereditary hemochromatosis, Costello et al 2004) and neurological disorders associated with movement disorder such as Parkinson's disease (PD; Péran et al 2010), manganese poisoning (Guilarte 2010) and Wilson's disease (Das and Ray 2006). Specifically, PD is a progressive neurodegenerative disorder clinically characterized by movement disorder (Jankovic 2008) as a result of the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) (Forno 1996).…”

Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells

“…However, chronic exposure to Mn may lead to a syndrome known as manganism, characterized by symptoms similar to idiopathic Parkinson's disease [4,5]. Many studies have revealed that neuronal apoptosis plays an important role in the Mn neurotoxicity [4,5].…”

Effects of Manganese Exposure on Blood Iron Indices in Miners of Iran Manganese Mines Co. (Qom)

“…Mn in high concentrations has pathological effects, especially its accumulation in central nervous system cause condition that is called manganism [5]. Manganism cause different nervous damages with Parkinson like symptoms such as tremor, imbalance and muscular spasm [4,6]. In addition it is revealed high Mn concentration in blood has influences on other organs such as liver [7].…”