title: Manganese-induced atypical parkinsonism is associated with altered Basal Ganglia activity and changes in tissue levels of monoamines in the rat.
abstract: Manganese neurotoxicity is associated with motor and cognitive disturbances known as Manganism. However, the mechanisms underlying these deficits remain unknown. Here we investigated the effects of manganese intoxication on motor and non-motor parkinsonian-like deficits such as locomotor activity, motor coordination, anxiety and "depressive-like" behaviors. Then, we studied the impact of this intoxication on the neuronal activity, the globus pallidus (GP) and subthalamic nucleus (STN). At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, norepinephrine and serotonin) has been determined. The experiments were carried out in adult Sprague-Dawley rats, daily treated with MnCl2 (10 mg/kg/, i.p.) for 5 weeks. We show that manganese progressively reduced locomotor activity as well as motor coordination in parallel with the manifestation of anxiety and "depressive-like" behaviors. Electrophysiological results show that, while majority of GP and STN neurons discharged regularly in controls, manganese increased the number of GP and STN neurons discharging irregularly and/or with bursts. Biochemical results show that manganese significantly decreased tissue levels of norepinephrine and serotonin with increased metabolism of dopamine in the striatum. Our data provide evidence that manganese intoxication is associated with impaired neurotransmission of monoaminergic systems, which is at the origin of changes in basal ganglia neuronal activity and the manifestation of motor and non-motor deficits similar to those observed in atypical Parkinsonism.
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; Université Mohamed V-Agdal, Faculté des Sciences, Equipe Rythmes Biologiques, Neurosciences et Environnement, Rabat, Morocco.
authors.forename: Safa
authors.initials: S
authors.lastname: Bouabid
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Delaville
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: De Deurwaerdère
authors.affiliation: Université Mohamed V-Agdal, Faculté des Sciences, Equipe Rythmes Biologiques, Neurosciences et Environnement, Rabat, Morocco.
authors.forename: Nouria
authors.initials: N
authors.lastname: Lakhdar-Ghazal
authors.affiliation: Univ. 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
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001479:Basal Ganglia / Q000187:drug effects / Q000473:pathology*; D001835:Body Weight / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D005917:Globus Pallidus / Q000187:drug effects / Q000473:pathology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008345:Manganese / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism*; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D012701:Serotonin; D008345:Manganese; D004298:Dopamine; D009638:Norepinephrine