Manganese Neurotoxicity: An Update of Pathophysiologic Mechanisms

@article{Normandin2004ManganeseNA,
  title={Manganese Neurotoxicity: An Update of Pathophysiologic Mechanisms},
  author={Louise Normandin and Alan S. Hazell},
  journal={Metabolic Brain Disease},
  year={2004},
  volume={17},
  pages={375-387}
}
The central nervous system, and the basal ganglia in particular, is an important target in manganese neurotoxicity, a disorder producing neurological symptoms similar to that of Parkinson's disease. Increasing evidence suggests that astrocytes are a site of early dysfunction and damage; chronic exposure to manganese leads to selective dopaminergic dysfunction, neuronal loss, and gliosis in basal ganglia structures together with characteristic astrocytic changes known as Alzheimer type II… 
Manganese neurotoxicity: behavioral disorders associated with dysfunctions in the basal ganglia and neurochemical transmission
TLDR
The collected data from recent available studies in humans and experimental animal models provide new information about the mechanisms by which Mn affects behavior, neurotransmitters, and basal ganglia function observed in manganism.
Manganese-Induced Parkinsonism and Parkinson’s Disease: Shared and Distinguishable Features
TLDR
The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn, and reviews occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking.
Manganese accumulation in the CNS and associated pathologies
TLDR
It is necessary to find an effective therapeutic strategy to decrease Mn levels in exposed individuals and to treat Mn long term effects, and in the case of patients with chronic liver failure it would be worthwhile to test a low-Mn diet in order to ameliorate symptoms of hepatic encephalopathy possibly related to Mn accumulation.
Manganese in Neurodegeneration
TLDR
Basic concepts on the essentiality and function of Mn as well as its mechanisms of neurodegeneration are reviewed.
Ultrastructural study of the hypothalamus in mice chronically treated with manganese
TLDR
The results suggest that the neurotoxic effect of Mn increases as time of exposure passes and produces ultrastructural alterations of nerve cells in the hypothalamus.
Effect of mitochondrial toxins on evoked somatosensory activity in rats
TLDR
The two mitochondrial toxins studied seem to exert their action centrally, primarily on synaptic transmission, rather than peripherally, and Recording of evoked activity could be used to follow-up the nervous system effects of mitochondrial toxins, but it requires further investigation.
Estrogen Attenuates Manganese-Induced Glutamate Transporter Impairment in Rat Primary Astrocytes
TLDR
The hypothesis that 17β-Estradiol and related compounds, such as tamoxifen may offer a potential therapeutic modality in neurodegenerative disorders, which are characterized by altered glutamate homeostasis is advanced.
Estrogen and tamoxifen reverse manganese‐induced glutamate transporter impairment in astrocytes
TLDR
The present study is the first to show that both E2 and TX effectively reverse Mn‐induced glutamate transport inhibition by restoring its expression and activity, thus offering a potential therapeutic modality in neurodegenerative disorders characterized by altered glutamate homeostasis.
...
...

References

SHOWING 1-10 OF 112 REFERENCES
Oxidative Stress Involves in Astrocytic Alterations Induced by Manganese
TLDR
Dysfunction of astrocytes possibly involved in neurotoxic action of manganese is suggested, because Astrocytes are central component of the brain's antioxidant defense.
Manganese Injection into the Rat Striatum Produces Excitotoxic Lesions by Impairing Energy Metabolism
TLDR
The results show that Mn may produce neuronal degeneration by an indirect excitotoxic process secondary to its ability to impair oxidative energy metabolism, similar to that found with two characterized mitochondrial toxins, aminooxyacetic acid, and 1-methyl-4-phenylpyridinium.
Manganese Decreases Glutamate Uptake in Cultured Astrocytes
TLDR
The results suggest a pathogenetic role for manganese in HE, possibly involving glutamate transport, and a combination of 5 mM NH4Cl with 100 μMManganese produced an additive effect on uptake inhibition.
Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes
TLDR
Data suggest that free radicals inhibit glutamate uptake primarily by long-lasting oxidation of protein sulfhydryl (SH) groups, and chemical modifiers of free SH groups, such as p-chloromercuribenzoate and N-ethylmaleimide, also induce uptake inhibition.
Selective vulnerability of pallidal neurons in the early phases of manganese intoxication
TLDR
Strikingly, manganese-treated GP cells – but not striatal ones – manifested peculiar responses to glutamate, since repeated applications of the excitatory amino acid, at concentrations which commonly promote desensitizing responses, produced instead an irreversible cell damage.
Chronic manganese poisoning: A neuropathological study with determination of manganese distribution in the brain
TLDR
The continuance of neurological disorders in CMP is not linked to an elevated manganese concentration itself in the brain, and CMP appears to be different from PD in neuropathology andManganese behavior in brain.
Manganese Augments Nitric Oxide Synthesis in Murine Astrocytes: A New Pathogenetic Mechanism in Manganism?
TLDR
The observations suggest that besides the known inhibition of mitochondrial function the neurotoxic effect of manganese in low concentrations might be mediated by the increased production of nitric oxide in astrocytes.
Manganese poisoning and the attack of trivalent manganese upon catecholamines.
...
...