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.

SLC30A10 transporter in the digestive system regulates brain manganese under basal conditions while brain SLC30A10 protects against neurotoxicity

“…The first line of evidence in support of the above idea comes from the fact that manganese levels in the brain, but not the liver, of the endoderm-specific knockouts were lower than whole-body knockouts, and only whole-body knockouts developed manganese-induced neurobehavioral deficits. In prior studies, WT rodents exposed to elevated manganese exhibited reduced movement in the open-field test (36,45,46) and had a lower latency to fall off the rotarod (45,47,48). Reduced movement of the whole-body Slc30a10 knockouts in the open-field test observed here is consistent with prior work.…”

Cytotoxic mechanism related to dihydrolipoamide dehydrogenase in Leydig cells exposed to heavy metals

“…All experiments were conducted according to the guidelines for animal care and use of China and were approved by the animal ethics committee of the Chinese Academy of Medical Science. The rats were divided into different groups: normal control rats were treated with water by gavage or intraperitoneal injection; Pb treatment rats were treated with Lead acetate(II) trihydrate (Sigma, St. Louis, MO, USA) by gavage (10 mg/kg and 25 mg/kg) for 10 w (Lu et al, 2014); Cd treatment rats were treated with cadmium chloride (Sigma, St. Louis, MO, USA) by gavage (5 mg/kg and 25 mg/kg) for 7 w (Lee et al, 2014); Mn treatment rats were intraperitoneally injected with manganese chloride (5 mg/kg and 10 mg/kg, Sigma, St. Louis, MO, USA) for 7 w (Bouabid et al, 2014). In order to determine the treatment period, testosterone in serum of rats were checked every week (data no shown here).…”

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

“…In addition, altered DA metabolism, altered neuronal activity (e.g. irregular firing of neurons) and changes in norepinephrine and serotonin levels in the brain have been reported in a study (Bouabid et al, 2014). On the other hand, in nonhuman primates, the main key event observed after Mn exposure is the reduced dopamine release in the striatum, which might be a result of Mn binding to DAT Guilarte et al, 2008;Guilarte et al, 2006).…”

“…Subsequently, locomotor deficits in rats as well as in nonhuman primates are often observed after Mn i.p. or inhalation exposure (Bouabid et al, 2014;Guilarte et al, 2006;Normandin et al, 2004;Witholt et al, 2000). Depressive-like behaviours in rats after Mn exposure have also been reported (Bouabid et al, 2014).…”