Axonal transport of manganese and its relevance to selective neurotoxicity in the rat basal ganglia

Sloot, W.N.; Gramsbergen, Jan-Bert P.

doi:10.1016/0006-8993(94)90959-8

Cited by 197 publications

(125 citation statements)

References 43 publications

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“…It could be that DAT blockade in this brain region causes an alteration in DMT-1 functioning thereby decreasing regional Mn transport, but this remains to be elucidated. A more likely scenario, albeit speculative, is that during Mn toxicity, the DAT facilitates Mn transport into striatal neurons (caudate putamen) and the Mn accumulates in the globus pallidus via axonal transport (Murayama et al, 2006;Sloot and Gramsbergen, 1994). Thus, blockade of the DAT in the caudate putamen attenuates this accumulation of Mn in striatal neurons due to chronic Mn exposure ultimately causing decreased Mn concentrations in the globus pallidus.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

Anderson

Cooney

Erikson

2007

Environmental Toxicology and Pharmacology

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Manganese (Mn) is an essential nutrient, though exposure to high concentrations may result in neurotoxicity characterized by alterations in dopamine neurobiology. To date, it remains elusive how and why Mn targets dopaminergic neurons although recently the role of the dopamine transporter has been suggested. Our primary goal of this study was to examine the potential roles of the monoamine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET), in neuronal Mn transport. Using striatal synaptosomes, we found that only inhibition of DAT significantly decreased Mn accumulation. Furthermore, weanling rats chronically exposed to Mn, significantly accumulated Mn in several brain regions. However, rats receiving the specific DAT inhibitor GBR12909 (1 mg/kg bw, three times/week; four weeks) had significantly lower Mn levels only in the globus pallidus compared to saline-treated rats (p<0.05). Our data show that inhibition of DAT exclusively inhibits Mn accumulation in the globus pallidus during chronic exposure.

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Section: Discussionmentioning

confidence: 99%

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

Anderson

Cooney

Erikson

2007

Environmental Toxicology and Pharmacology

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“…Support for receptor-mediated endocytosis of a Mn-Tf complex in cultured neuroblastoma cells (SHSY5Y) was recently demonstrated by Suarez and Eriksson (1993). Sloot and Gramsbergen (1994) have demonstrated anterograde axonal transport of 54 Mn in both nigrostriatal and striatonigral pathways. Furthermore, in vivo, intravenous administration of ferric-hydroxide dextran complex significantly inhibits Mn brain uptake, and high Fe intake reduces CNS Mn concentrations, corroborating a relationship between Fe and Mn transport (Aschner and Aschner, 1990;Diez-Ewald et al, 1968).…”

Section: Manganese Transport Into Brain Transferrin/transferrin Recepmentioning

confidence: 90%

“…Interestingly, Fe concentrations in these structures are the highest as well (Hill and Switzer, 1984). Although the areas with dense Tf distribution (Hill et al, 1985) do not correspond to the distribution of Mn (or Fe), the fact that Mnaccumulating areas are efferent to areas of high Tf receptor density suggests that these sites may accumulate Mn through neuronal transport (Sloot and Gramsbergen, 1994). For example, the Mn rich areas of the ventral-pallidum, globus pallidus, and substantia nigra receive input from the nucleus accumbens and the caudate-putamen (Walaas and Fonnum, 1979;Nagy et al, 1978) -two areas abundantly rich in Tf receptors.…”

Section: Manganese Transport Into Brain Transferrin/transferrin Recepmentioning

confidence: 98%

Manganese neurotoxicity: A focus on the neonate

Erikson

Thompson

Aschner

et al. 2007

Pharmacology & Therapeutics

224

141

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Manganese (Mn) is an essential trace metal found in all tissues, and it is required for normal amino acid, lipid, protein, and carbohydrate metabolism. While Mn deficiency is extremely rare in humans, toxicity due to overexposure of Mn is more prevalent. The brain appears to be especially vulnerable. Mn neurotoxicity is most commonly associated with occupational exposure to aerosols or dusts that contain extremely high levels (> 1-5 mg Mn/m 3 ) of Mn, consumption of contaminated well water, or parenteral nutrition therapy in patients with liver disease or immature hepatic functioning such as the neonate. This review will focus primarily on the neurotoxicity of Mn in the neonate. We will discuss putative transporters of the metal in the neonatal brain and then focus on the implications of high Mn exposure to the neonate focusing on typical exposure modes (e.g., dietary and parenteral). Although Mn exposure via parenteral nutrition is uncommon in adults, in premature infants, it is more prevalent, so this mode of exposure becomes salient in this population. We will briefly review some of the mechanisms of Mn neurotoxicity and conclude with a discussion of ripe areas for research in this underreported area of neurotoxicity.

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“…Upon intracerebral injection, the paramagnetic ion manganese (Mn 2 + ) acts as a neuronal tracer, as it enters neurons through Ca 2 + channels and moves along axons (Pautler et al, 1998;Sloot and Gramsbergen, 1994). In addition, manganese can be transported transsynaptically (Pautler et al, 1998;Saleem et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Manganese-Enhanced MRI of Brain Plasticity in Relation to Functional Recovery after Experimental Stroke

Zijden

Bouts

et al. 2007

J Cereb Blood Flow Metab

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Restoration of function after stroke may be associated with structural remodeling of neuronal connections outside the infarcted area. However, the spatiotemporal profile of poststroke alterations in neuroanatomical connectivity in relation to functional recovery is still largely unknown. We performed in vivo magnetic resonance imaging (MRI)-based neuronal tract tracing with manganese in combination with immunohistochemical detection of the neuronal tracer wheatgerm agglutinin horseradish peroxidase (WGA-HRP), to assess changes in intra-and interhemispheric sensorimotor network connections from 2 to 10 weeks after unilateral stroke in rats. In addition, functional recovery was measured by repetitive behavioral testing. Four days after tracer injection in perilesional sensorimotor cortex, manganese enhancement and WGA-HRP staining were decreased in subcortical areas of the ipsilateral sensorimotor network at 2 weeks after stroke, which was restored at later time points. At 4 to 10 weeks after stroke, we detected significantly increased manganese enhancement in the contralateral hemisphere. Behaviorally, sensorimotor functions were initially disturbed but subsequently recovered and plateaued 17 days after stroke. This study shows that manganese-enhanced MRI can provide unique in vivo information on the spatiotemporal pattern of neuroanatomical plasticity after stroke. Our data suggest that the plateau stage of functional recovery is associated with restoration of ipsilateral sensorimotor pathways and enhanced interhemispheric connectivity.

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Axonal transport of manganese and its relevance to selective neurotoxicity in the rat basal ganglia

Cited by 197 publications

References 43 publications

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

Manganese neurotoxicity: A focus on the neonate

Manganese-Enhanced MRI of Brain Plasticity in Relation to Functional Recovery after Experimental Stroke

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