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.
Highlights
Manganese (Mn) is an essential trace element that is naturally present in water, air, soil and food
The present study shows for the first time that Mn intoxication induced motor and non-motor deficits paralleled by dramatic changes in the firing rate and patterns of globus pallidus (GP) and subthalamic nucleus (STN) neurons and decreased tissue levels of norepinephrine and serotonin, in addition to an increase of dopamine metabolism
We show that Mn intoxication induced a progressive slowing of body weight gain, in line with previous studies [26,44,45,46]
Summary
Manganese (Mn) is an essential trace element that is naturally present in water, air, soil and food It plays an important role in the development and functioning of the brain as it is a co-factor for several enzymes involved in neurotransmitter synthesis and metabolism [1,2]. A decrease in tissue levels of NE and 5-HT has been reported in non-human primates exposed to Mn [23,24] Together, these studies suggested that Mn alters the integrity of monoaminergic neurotransmission. We hypothesized that Mn exposure could induce defective monoaminergic neurotransmission resulting in a disorganization of the neuronal activity of GP and STN, which might be at the origin of motor and non-motor deficits
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