title: Manganese neurotoxicity: behavioral disorders associated with dysfunctions in the basal ganglia and neurochemical transmission.
abstract: Manganese (Mn) is an essential element required for many physiological functions. While it is essential at physiological levels, excessive accumulation of Mn in the brain causes severe dysfunctions in the central nervous system known as manganism. Manganism is an extrapyramidal disorder characterized by motor disturbances associated with neuropsychiatric and cognitive disabilities similar to Parkinsonism. As the primary brain regions targeted by Mn are the basal ganglia, known to be involved in the pathophysiology of extrapyramidal disorders, this review will examine the impact of Mn exposure on the basal ganglia circuitry and neurotransmitters in relation to motor and non-motor disorders. 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. The effects of the alterations of metals on basal ganglia and neurochemical functioning are critical to develop effective modalities not only for the treatment of vulnerable populations (e.g., Mn-exposed workers) but also for understanding the etiology of neurodegenerative diseases where brain metal imbalances are involved, such as Parkinson's disease. We examine the impact of manganese (Mn) exposure on the basal ganglia circuitry and neurotransmitters in relation with motor and non-motor disorders. The collected data from available studies show that when accumulated in the globus pallidus, Mn influences the subthalamic (STN) and substantia nigra (SN) neurons, which are at the origin of changes in the thalamus and the cortex.
authors.affiliation: University de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.|Université Mohammed V, Faculté des Sciences, Equipe Rythmes Biologiques, Neurosciences et Environnement, Rabat, Morocco.
authors.forename: Safa
authors.initials: S
authors.lastname: Bouabid
authors.affiliation: University de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.|Université Mohammed V, Faculté des Sciences, Equipe Rythmes Biologiques, Neurosciences et Environnement, Rabat, Morocco.
authors.forename: Anass
authors.initials: A
authors.lastname: Tinakoua
authors.affiliation: Université Mohammed V, Faculté des Sciences, Equipe Rythmes Biologiques, Neurosciences et Environnement, Rabat, Morocco.
authors.forename: Nouria
authors.initials: N
authors.lastname: Lakhdar-Ghazal
authors.affiliation: University de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Benazzouz
keywords: Parkinson's disease; basal ganglia functions; manganese neurotoxicity; monoamine neurotransmission; motor deficits; non-motor disorders