Manganese neurotoxicity: Effects ofl-DOPA and pargyline treatments

Parenti, Marco; Flauto, C.; Parati, Eugenio; Vescovi, Angelo L.; Groppetti, A.

doi:10.1016/0006-8993(86)91571-4

Cited by 46 publications

(23 citation statements)

References 24 publications

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“…Of these regions, the globus pallidus appears to be affected the most, a feature of Mn neurotoxicity that is distinct from Parkinsonism (Verity, 1999). Nevertheless, studies show that dopamine (DA), the principal neurotransmitter that is severely reduced in the striatum of Parkinson's disease patients, is also reduced by Mn both in vivo (Parenti et al, 1986) and in vitro (Vescovi et al, 1991) exposure paradigms. This reduction of DA may be due, at least in part, to direct oxidation of this neurotransmitter by Mn (Donaldson et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Sistrunk

Ross

Filipov

2007

Environmental Toxicology and Pharmacology

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Following combustion of fuel containing the additive methylcyclopentadienyl-manganesetricarbonyl (MMT), manganese phosphate (MnPO 4 ) and manganese sulfate (MnSO 4 ) are emitted in the atmosphere. Manganese chloride (MnCl 2 ), another Mn 2+ species, is widely used experimentally. Using rat striatal slices, we found that MnPO 4 decreased tissue and media dopamine (DA) and media Dopac (a DA metabolite) levels substantially more than either MnCl 2 or MnSO 4 ; antioxidants were partially protective. Also, both MnCl 2 and MnPO 4 (more potently) oxidized DA and Dopac even in the absence of tissue in the media, suggesting a direct interaction between Mn and DA/Dopac. Because aminochrome is a major oxidation product of DA, we next determined whether MnPO 4 will be more potent in forming aminochrome than MnCl 2 or MnSO 4 which, indeed, was the case. Thus, a potential additional mechanism for the neurotoxic effects of environmentally-relevant forms of Mn, MnPO 4 in particular, is the generation of reactive DA intermediates.

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Section: Introductionmentioning

confidence: 99%

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Sistrunk

Ross

Filipov

2007

Environmental Toxicology and Pharmacology

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“…In previous studies the turning behavior was caused by unilateral injections of hundreds of nmol of Mn 2+ (Parenti et al, 1986, Ponzoni et al, 2000, Fernandes et al, 2010. In another study an 8 nmol dose, but of Mn 3+ , did cause a significant impairment of spontaneous motor activity and conditioned avoidance response two weeks after an intranigral administration (Diaz-Veliz et al, 2004).…”

mentioning

confidence: 87%

Imaging neuronal pathways with 52Mn PET: Toxicity evaluation in rats

et al. 2017

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Manganese in its divalent state (Mn 2+ ) has features that make it a unique tool for tracing neuronal pathways. It is taken up and transported by neurons in an activity dependent manner and it can cross synapses. It also acts as a contrast agent for magnetic resonance imaging (MRI) enabling visualization of neuronal tracts. However, due to the limited sensitivity of MRI systems relatively high Mn 2+ doses are required. This is undesirable, especially in long-term studies, because of the known toxicity of the metal.In order to overcome this limitation, we propose 52 Mn as a positron emission tomography (PET) neuronal tract tracer. We used 52 Mn for imaging dopaminergic pathways after a unilateral injection into the ventral tegmental area (VTA), as well as the striatonigral pathway after an injection into the dorsal striatum (STR) in rats. Furthermore, we tested potentially noxious effects of the radioactivity dose with a behavioral test and histological staining. 24 h after 52 Mn administration, the neuronal tracts were clearly visible in PET images and statistical analysis confirmed the observed distribution of the tracer. We noticed a behavioral impairment in some animals treated with 170 kBq of 52 Mn, most likely caused by dysfunction of dopaminergic cells. Moreover, there was a substantial DNA damage in the brain tissue after applying 150 kBq of the tracer. However, all those effects were completely eliminated by reducing the 52 Mn dose to 20-30 kBq. Crucially, the reduced dose was still sufficient for PET imaging.

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“…O efeito seletivo da 6-OHDA sobre os neurônios catecolaminérgicos é resultante de sua analogia estrutural às catecolaminas e desta forma é captada por estes neurônios através do sistema de transporte de alta afinidade presente em seus terminais 24 . A ação tóxica da 6-OHDA sobre o sistema catecolaminérgico, especificamente o dopaminérgico, poderia ser mediada por: a) sua capacidade em potenciar o mecanismo autoxidativo da DA com a concomitante produção de radicais livres; b) produção de quinonas durante a sua oxidação, as quais poderiam ligar-se covalentemente aos grupos sulfidrilas das células.…”

Section: 45-trihidroxifeniletilamina (6-hidroxidopamina6-ohdâ)unclassified

“…O efeito é dose-dependente, observando-se também redução nas concentrações de DOPAC o que sugere a existência de inibição na síntese do neurotransmissor ou degeneração dos neurônios dopaminérgicos 24 . A aplicação unilaretal de MnCl, na substância negra de ratos tem demonstrado resposta imunocitoquímica à enzima tirosina hidroxilase (TH) e à apomorfina, dose-dependentes.…”

Section: Manganêsunclassified

Neurobiologia do parkinsonismo: II. modelos experimentais

Ponzoni¹,

Garcia-Cairasco²

1995

Arq. Neuro-Psiquiatr.

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RESUMO -O emprego de modelos experimentais de parkinsonismo tem contribuído não só para explicar o conhecimento das funções dos gânglios basais como também tem permitido o surgimento de várias hipóteses para explicar os processos neurodegeneratives do sistema nervoso central. Nesta revisão são apresentados e discutidos os modelos de parkinsonismo que utilizam neurotoxins como a 6-hidroxidopamina, MPTP e o manganês.PALAVRAS-CHAVE: parkinsonismo, 6-hidroxidopamina, MPTP, manganês, modelos experimentais. Neurobiology of parkinsonism: II. Experimental modelsSUMMARY -The study of experimental models of parkinsonism has contributed to the knowledge of basal ganglia functions, as well as to the establishment of several hypothesis for the explanation of the cause and expression of central neurodegenerative disorders. In this review we present and discuss several models such as 6-hydroxydopamine, MPTP and manganese, all of them widely used to characterize the behavioral, cellular and molecular mechanisms of parkinsonism.

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Manganese neurotoxicity: Effects ofl-DOPA and pargyline treatments

Cited by 46 publications

References 24 publications

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Imaging neuronal pathways with 52Mn PET: Toxicity evaluation in rats

Neurobiologia do parkinsonismo: II. modelos experimentais

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