Manganese-induced atypical parkinsonism is associated with altered Basal Ganglia activity and changes in tissue levels of monoamines in the rat.
PLoS ONE. 2014-06-04; 9(6): e98952
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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.