title: Manganese neurotoxicity: an update of pathophysiologic mechanisms.
abstract: 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 astrocytosis. Astrocytes possess a high affinity, high capacity, specific transport system for manganese facilitating its uptake, and sequestration in mitochondria, leading to a disruption of oxidative phosphorylation. In addition, manganese causes a number of other functional changes in astrocytes including an impairment of glutamate transport, alterations of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, production of nitric oxide, and increased densities of binding sites for the "peripheral-type" benzodiazepine receptor (a class of receptor predominantly localized to mitochondria of astrocytes and involved in oxidative metabolism, mitochondrial proliferation, and neurosteroid synthesis). Such effects can lead to compromised energy metabolism, resulting in altered cellular morphology, production of reactive oxygen species, and increased extracellular glutamate concentration. These consequences may result in impaired astrocytic-neuronal interactions and play a major role in the pathophysiology of manganese neurotoxicity.
authors.affiliation: Department of Medicine, Hôpital Saint-Luc (CHUM), University of Montreal, Montreal, Quebec, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Normandin
authors.forename: Alan S
authors.initials: AS
authors.lastname: Hazell
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D004781:Environmental Exposure; D006801:Humans; D020149:Manganese Poisoning / Q000150:complications*; D009435:Synaptic Transmission