maneb and Parkinson-Disease--Secondary

The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low-dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pesticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration.

Topics: Animals; Apoptosis; Dieldrin; Environmental Exposure; Humans; Maneb; Neurodegenerative Diseases; Organophosphates; Oxidative Stress; Paraquat; Parkinson Disease, Secondary; Pesticides; Proteasome Inhibitors; Pyrethrins

Parkinson's disease (PD) is a common neurodegenerative disorder largely of idiopathic nature with the exceptions of rare familial forms, and is characterized by both motor and non-motor disturbances. Pathologically, most motor features are the result of a dramatic loss of ventral tier mesencephalic dopaminergic neurons and thus dopamine content at their target sites. Although the exact etiology of the disease remains to be elucidated, it is thought to be multifactorial, with a critical role for environmental factors, such as pesticides, that may act on genetically predisposed individuals. Arising from consideration of the potential environmental triggers of PD, in vivo animal models of the disease utilizing these compounds are increasingly reported in the literature. Here, we review recent advances in the predominant models employing the insecticide Rotenone, the herbicide Paraquat and the fungicide Maneb, discuss their scientific merit and evaluate their relevance in the study of PD pathogenesis.

Topics: Animals; Disease Models, Animal; Environmental Exposure; Humans; Maneb; Paraquat; Parkinson Disease, Secondary; Pesticides; Rotenone

Parkinson's disease is a progressive neurological disorder associated with selective degeneration of nigrostriatal dopaminergic neurons. It is the most common of the neurodegenerative movement disorders, affecting approximately 1% of the population over age 65. Though the exact cause of the neurodegeneration is unknown, it has been shown that environmental factors can contribute to the onset of Parkinson's disease. Parkinsonian symptoms are seen following exposure to the herbicide paraquat, and the fungicide maneb. Furthermore, evidence clearly shows that neurodegeneration develops in environments where workers are co-exposed to paraquat and maneb. These neurotoxins cause a pesticide-induced loss of dopaminergic neurons, inducing a Parkinsonian phenotype. The specific mechanisms by which these environmental neurotoxins affect the nigral dopaminergic neurons are unknown. This gap in mechanistic understanding raises a need for further examination of their cytotoxic effects. Despite advances in pharmacotherapy that have improved quality of life, the mortality rate among Parkinson's disease sufferers remains largely unchanged. There is need for a proactive treatment strategy that could provide neuroprotection or neurorestoration. Since evidence has shown that environmental neurotoxins play an important role in nigral degeneration, there is obviously a need to take a closer look at such toxins since a greater understanding could aid in development of novel pharmacological agents with anti-parkinson and neuroprotective effects. In this review, we intend to examine the role of environmental toxins, namely paraquat and maneb, in the neurotoxicity that leads to dopamine depletion.

Topics: Animals; Apoptosis; Drug Interactions; Fungicides, Industrial; Herbicides; Humans; Inflammation; Maneb; Mitochondria; Necrosis; Neurotoxicity Syndromes; Oxidative Stress; Paraquat; Parkinson Disease, Secondary

Beyond nigrostriatal dopaminergic system, the noradrenergic locus coeruleus (LC/NE) neurons are also degenerated in patients with Parkinson's disease (PD), the second most common neurodegenerative disorder. We previously reported that microglia-mediated neuroinflammation contributes to LC/NE neurodegeneration. The purpose of this study is aimed to test whether taurine, an endogenous amino acid, could be able to protect LC/NE neurons through inhibition of microglial activation using paraquat and maneb-induced mouse PD model. Taurine (150 mg/kg) was administrated (i.p) to mice 30 min prior to paraquat (10 mg/kg) and maneb (30 mg/kg) intoxication for consecutive 6 weeks (twice per week). The results clearly demonstrated that paraquat and maneb co-exposure resulted in loss of tyrosine hydroxylase-positive neurons in the LC in mice, which was significantly ameliorated by taurine. Mechanistically, inhibition of microglia-mediated neuroinflammation contributed to taurine-afforded neuroprotection. Taurine attenuated paraquat and maneb-induced microglial activation and M1 polarization as well as release of proinflammatory cytokines in brainstem of mice. Taurine also abrogated microglial NADPH oxidase activation and oxidative damage in paraquat and maneb-treated mice. Furthermore, inhibition of nuclear factor-κB (NF-κB) but not signal transducers and activators of transcription 1/3 (STAT1/3) signaling pathway participated in taurine-inhibited microglial activation. Collectively, taurine exerted LC/NE neuroprotection against microglia-mediated neurotoxicity. The robust neuroprotective effects of taurine suggest that taurine may be a promising candidate for potential therapy for patients suffering from PD.

Topics: Animals; Locus Coeruleus; Male; Maneb; Mice; Microglia; NADPH Oxidases; Neurons; Neuroprotective Agents; Paraquat; Parkinson Disease, Secondary; STAT1 Transcription Factor; STAT3 Transcription Factor; Taurine

Microglia-mediated neuroinflammation is implicated in multiple neurodegenerative disorders, including Parkinson's disease (PD). Hence, the modulatioein of sustained microglial activation may have therapeutic potential. This study is designed to test the neuroprotective efficacy of taurine, a major intracellular free β-amino acid in mammalian tissues, by using paraquat and maneb-induced PD model. Results showed that mice intoxicated with paraquat and maneb displayed progressive dopaminergic neurodegeneration and motor deficits, which was significantly ameliorated by taurine. Taurine also attenuated the aggregation of α-synuclein in paraquat and maneb-intoxicated mice. Mechanistically, taurine suppressed paraquat and maneb-induced microglial activation. Moreover, depletion of microglia abrogated the dopaminergic neuroprotective effects of taurine, revealing the role of microglial activation in taurine-afforded neuroprotection. Subsequently, we found that taurine suppressed paraquat and maneb-induced microglial M1 polarization and gene expression levels of proinflammatory factors. Furthermore, taurine was shown to be able to inhibit the activation of NADPH oxidase (NOX2) by interfering with membrane translocation of cytosolic subunit, p47

Topics: alpha-Synuclein; Animals; Disease Models, Animal; Dopaminergic Neurons; Gait; Gene Expression; Male; Maneb; Mice; Mice, Inbred C57BL; Microglia; NADPH Oxidase 2; NADPH Oxidases; Neuroprotective Agents; NF-kappa B; Paraquat; Parkinson Disease, Secondary; Signal Transduction; Taurine

Paraquat (PQ) and maneb (MB) are able to induce neurotoxic effects by promoting α-synuclein (α-syn) aggregates and altering tyrosine hydroxylase (TH), thus increasing the risk of Parkinson's disease (PD). These pesticides promote neurotoxic effects also by affecting proteasome function that normally regulate protein turnover. We investigated the effects of the two pesticides exposure on multiple targets involved in PD, using SH-SY5Y cells. First, we evaluated TH and α-syn protein levels following PQ and MB cell exposure and a significant increase of these protein levels was observed. Subsequently, since a relationship between ubiquitin/proteasome and opioid receptors has been proposed, the effects of pesticides on their gene expression have been investigated. A decrease of β1 and Rpt3 proteasome subunit mRNA levels, together with the μ and δ opioid receptor down-regulation, was detected. The reported alterations, here simultaneously observed, help to clarify the involvement of multiple biological markers implicated in PD, often separately evaluated.

Topics: alpha-Synuclein; ATPases Associated with Diverse Cellular Activities; Cell Line, Tumor; Cell Survival; Gene Expression Regulation, Neoplastic; Humans; Insecticides; Maneb; Models, Biological; Neuroblastoma; Paraquat; Parkinson Disease, Secondary; Proteasome Endopeptidase Complex; Receptors, Opioid; Tyrosine 3-Monooxygenase

The neurodegenerative effects of Parkinson's disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, which has been implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination.

Topics: Animals; Cell Death; Disease Models, Animal; Dopaminergic Neurons; Drosophila melanogaster; Maneb; Motor Activity; Paraquat; Parkinson Disease, Secondary; Pesticides; Survival Analysis; Ubiquitin-Protein Ligases; Ziram

Mitochondrial dysfunction is the foremost perpetrator of the nigrostriatal dopaminergic neurodegeneration leading to Parkinson's disease (PD). However, the roles played by majority of the mitochondrial proteins in PD pathogenesis have not yet been deciphered. The present study investigated the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and combined maneb and paraquat on the mitochondrial proteome of the nigrostriatal tissues in the presence or absence of minocycline, levodopa and manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP). The differentially expressed proteins were identified and proteome profiles were correlated with the pathological and biochemical anomalies induced by MPTP and maneb and paraquat. MPTP altered the expression of twelve while combined maneb and paraquat altered the expression of fourteen proteins. Minocycline, levodopa and MnTMPyP, respectively, restored the expression of three, seven and eight proteins in MPTP and seven, eight and eight proteins in maneb- and paraquat-treated groups. Although levodopa and MnTMPyP rescued from MPTP- and maneb- and paraquat-mediated increase in the microglial activation and decrease in manganese-superoxide dismutase expression and complex I activity, dopamine content and number of dopaminergic neurons, minocycline defended mainly against maneb- and paraquat-mediated alterations. The results demonstrate that MPTP and combined maneb and paraquat induce mitochondrial dysfunction and microglial activation and alter the expression of a bunch of mitochondrial proteins leading to the nigrostriatal dopaminergic neurodegeneration and minocycline, levodopa or MnTMPyP variably offset scores of such changes.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Antiparkinson Agents; Disease Models, Animal; Dopamine; Homeodomain Proteins; Levodopa; Male; Maneb; Metalloporphyrins; Mice; Microglia; Minocycline; Mitochondria; Paraquat; Parkinson Disease, Secondary; Proteome; Stathmin; Superoxide Dismutase

Maneb and paraquat are known to induce Parkinson's disease (PD) phenotype, however, caffeine offers neuroprotection. Nitric oxide (NO) acts an important mediator in PD phenotype and tyrosine kinase (TK), nuclear factor kappa B (NF-kB), p38 mitogen activated protein kinase (p38 MAPK) are known to regulate its production. The present study aimed to elucidate the role of caffeine in the regulation of NO production and microglial activation and their subsequent contribution in dopaminergic neuroprotection. The animals were treated with caffeine and/or maneb and paraquat along with controls. In a few sets of experiments, the animals were also treated with aminoguanidine, an inhibitor of inducible NO synthase, pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kB, genistein, an inhibitor of TK or SB202190, an inhibitor of p38 MAPK. Tyrosine hydroxylase (TH)-immunoreactivity and anti-integrin αM (OX-42) staining were performed to assess the number of dopaminergic neurons and activation of microglia, respectively. NO was measured in terms of nitrite, however, the expressions of p38 MAPK, interleukin (IL)-1β, NF-kB and TK were checked by western blot analyses. Maneb and paraquat induced the number of degenerating dopaminergic neurons, microglial cells, nitrite content, expressions of IL-1β, p38 MAPK, NF-kB and TK and caffeine co-treatment reduced the level of such alterations. Reductions were more pronounced in the animals co-treated with aminoguanidine, PDTC, genistein or SB202190. The results obtained thus demonstrate that caffeine down-regulates NO production, neuroinflammation and microglial activation, which possibly contribute to neuroprotection.

Topics: Animals; Caffeine; Inflammation Mediators; Male; Maneb; Mice; Neuroprotective Agents; Nitric Oxide; Paraquat; Parkinson Disease, Secondary; Phenotype

Parkinson's disease (PD) is a neurodegenerative disease in which the etiology of 90 percent of the patients is unknown. Pesticide exposure is a major risk factor for PD, and paraquat (PQ), pyridaben (PY) and maneb (MN) are amongst the most widely used pesticides. We studied mRNA expression using transcriptome sequencing (RNA-Seq) in the ventral midbrain (VMB) and striatum (STR) of PQ, PY and paraquat+maneb (MNPQ) treated mice, followed by pathway analysis. We found concordance of signaling pathways between the three pesticide models in both the VMB and STR as well as concordance in these two brain areas. The concordant signaling pathways with relevance to PD pathogenesis were e.g. axonal guidance signaling, Wnt/β-catenin signaling, as well as pathways not previously linked to PD, e.g. basal cell carcinoma, human embryonic stem cell pluripotency and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Human PD pathways previously identified by expression analysis, concordant with VMB pathways identified in our study were axonal guidance signaling, Wnt/β-catenin signaling, IL-6 signaling, ephrin receptor signaling, TGF-β signaling, PPAR signaling and G-protein coupled receptor signaling. Human PD pathways concordant with the STR pathways in our study were Wnt/β-catenin signaling, axonal guidance signaling and G-protein coupled receptor signaling. Peroxisome proliferator activated receptor delta (Ppard) and G-Protein Coupled Receptors (GPCRs) were common genes in VMB and STR identified by network analysis. In conclusion, the pesticides PQ, PY and MNPQ elicit common signaling pathways in the VMB and STR in mice, which are concordant with known signaling pathways identified in human PD, suggesting that these pathways contribute to the pathogenesis of idiopathic PD. The analysis of these networks and pathways may therefore lead to improved understanding of disease pathogenesis, and potential novel therapeutic targets.

Topics: Animals; Corpus Striatum; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; Maneb; Mesencephalon; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Paraquat; Parkinson Disease; Parkinson Disease, Secondary; Pesticides; Pyridazines; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transcriptome

Due to the heavy and expanding agricultural use of neurotoxic pesticides suspected to affect dopaminergic neurons, it is imperative to closely examine the role of pesticides in the development of Parkinson's disease (PD). We focus our investigation on pesticide use in California's heavily agricultural central valley by utilizing a unique pesticide use reporting system. From 2001 to 2007, we enrolled 362 incident PD cases and 341 controls living in the Central Valley of California. Employing our geographic information system model, we estimated ambient exposures to the pesticides ziram, maneb, and paraquat at work places and residences from 1974 to 1999. At workplaces, combined exposure to ziram, maneb, and paraquat increased risk of PD three-fold (OR: 3.09; 95% CI: 1.69, 5.64) and combined exposure to ziram and paraquat, excluding maneb exposure, was associated with a 80% increase in risk (OR:1.82; 95% CI: 1.03, 3.21). Risk estimates for ambient workplace exposure were greater than for exposures at residences and were especially high for younger onset PD patients and when exposed in both locations. Our study is the first to implicate ziram in PD etiology. Combined ambient exposure to ziram and paraquat as well as combined ambient exposure to maneb and paraquat at both workplaces and residences increased PD risk substantially. Those exposed to ziram, maneb, and paraquat together experienced the greatest increase in PD risk. Our results suggest that pesticides affecting different mechanisms that contribute to dopaminergic neuron death may act together to increase the risk of PD considerably.

Topics: Age Factors; California; Environmental Exposure; Female; Geographic Information Systems; Humans; Male; Maneb; Middle Aged; Occupational Exposure; Paraquat; Parkinson Disease, Secondary; Pesticides; Risk Factors; Smoking; Socioeconomic Factors; Ziram

The study aimed to investigate the involvement of nitric oxide (NO) in maneb (MB)- and paraquat (PQ)-induced Parkinson's disease (PD) phenotype in mouse and its subsequent contribution to lipid peroxidation. Animals were treated intraperitoneally with or without MB and PQ, twice a week for 3, 6 and 9 weeks. In some sets of experiments (9 weeks treated groups), the animals were treated intraperitoneally with or without inducible nitric oxide synthase (iNOS) inhibitor-aminoguanidine, tyrosine kinase inhibitor-genistein, nuclear factor-kappa B (NF-kB) inhibitor-pyrrolidine dithiocarbamate (PDTC) or p38 mitogen activated protein kinase (MAPK) inhibitor-SB202190. Nitrite content and lipid peroxidation were measured in all treated groups along with respective controls. RNA was isolated from the striatum of control and treated mice and reverse transcribed into cDNA. RT-PCR was performed to amplify iNOS mRNA and western blot analysis was done to check its protein level. MB- and PQ-treatment induced nitrite content, expressions of iNOS mRNA and protein and lipid peroxidation as compared with respective controls. Aminoguanidine resulted in a significant attenuation of iNOS mRNA expression, nitrite content and lipid peroxidation demonstrating the involvement of nitric oxide in MB- and PQ-induced lipid peroxidation. Genistein, SB202190 and PDTC reduced the expression of iNOS mRNA, nitrite content and lipid peroxidation in MB- and PQ-treated mouse striatum. The results obtained demonstrate that nitric oxide contributes to an increase of MB- and PQ-induced lipid peroxidation in mouse striatum and tyrosine kinase, p38 MAPK and NF-kB regulate iNOS expression.

Topics: Animals; Corpus Striatum; Guanidines; Lipid Peroxidation; Male; Maneb; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Nitrites; Paraquat; Parkinson Disease, Secondary; Pesticides; Phenotype; RNA, Messenger; Second Messenger Systems; Tyrosine 3-Monooxygenase

The neuroprotective effects of Polygonum multiflorum extract (PME) and its two fractions, ethanol-soluble PME (PME-I) and -insoluble PME (PME-II), on the degeneration of nigrostriatal dopaminergic neurons induced by a combination of paraquat and maneb (PQMB) were investigated in male C57BL/6 mice. The mice were treated twice a week for 6 weeks with intraperitoneal injections of PQMB. This combination caused a reduction of spontaneous locomotor activity, motor incoordination, and declines of dopamine level in the striatum and tyrosine hydroxylase-positive neurons in the substantia nigra. Administration of PME and PME-I once daily for 47 days during 6 weeks of PQMB treatment and last 8 days after PQMB significantly attenuated the impairment of behavioral performance and the decrease in striatal dopamine level and substantia nigral tyrosine hydroxylase-positive neurons in the PQMB-treated animals, whereas the administration of PME-II had no effect on these behavioral, neurochemical and histological indices. The present findings suggest that PME has a beneficial influence on parkinsonism induced by PQMB and that the effects of PME are attributable to some substance(s) included in the ethanol-soluble fraction of PME (PME-I).

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Antiparkinson Agents; Chromatography, High Pressure Liquid; Dopamine; Fungicides, Industrial; Herbicides; Immunohistochemistry; Levodopa; Male; Maneb; Mice; Mice, Inbred C57BL; Motor Activity; Neostriatum; Nerve Degeneration; Neuroprotective Agents; Paraquat; Parkinson Disease, Secondary; Phytotherapy; Plant Roots; Polygonum; Substantia Nigra; Tyrosine 3-Monooxygenase

While advancing age is the only unequivocally accepted risk factor for idiopathic Parkinson's disease, it has been postulated that exposure to environmental neurotoxicants combined with ageing could increase the risk for developing Parkinson's disease. The current study tested this hypothesis by exposing C57BL/6 mice that were 6 weeks, 5 months or 18 months old to the herbicide paraquat, the fungicide maneb or paraquat + maneb, a combination that produces a Parkinson's disease phenotype in young adult mice. Paraquat + maneb-induced reductions in locomotor activity and motor coordination were age dependent, with 18-month-old mice most affected and exhibiting failure to recover 24 h post-treatment. Three months post-treatment, reductions in locomotor activity and deficits in motor coordination were sustained in 5-month-old and further reduced in 18-month-old paraquat + maneb groups. Progressive reductions in dopamine metabolites and dopamine turnover were greatest in 18-month-old paraquat + maneb and paraquat groups 3 months post-treatment. Increased tyrosine hydroxylase enzyme activity compensated for striatal tyrosine hydroxylase protein and/or dopamine loss following treatment in 6-week-old and 5-month-old, but not 18-month-old paraquat and paraquat + maneb mice. Numbers of nigrostriatal dopaminergic neurons were reduced in all age groups following paraquat alone and paraquat + maneb exposure, but these losses, along with decreases in striatal tyrosine hydroxylase protein levels, were progressive in 18-month-old paraquat and paraquat + maneb groups between 2 weeks and 3 months post-exposure. Collectively, these data demonstrate enhanced sensitivity of the ageing nigrostriatal dopamine pathway to these pesticides, particularly paraquat + maneb, resulting in irreversible and progressive neurotoxicity.

Topics: Aging; Animals; Cell Count; Corpus Striatum; Disease Susceptibility; Dopamine; Drug Combinations; Glutamate Decarboxylase; Male; Maneb; Mice; Mice, Inbred C57BL; Motor Activity; Neurons; Neurotoxins; Paraquat; Parkinson Disease, Secondary; Phenotype; Serotonin; Substantia Nigra; Tyrosine 3-Monooxygenase

Experimental evidence supporting 1,1'-dimethyl-4,4'-bipyridinium [paraquat (PQ)] as a risk factor for Parkinson's disease (PD) is equivocal. Other agricultural chemicals, including dithiocarbamate fungicides such as manganese ethylenebisdithiocarbamate [maneb (MB)], are widely used in the same geographical regions as paraquat and also impact dopamine systems, suggesting that mixtures may be more relevant etiological models. This study therefore proposed that combined PQ and MB exposures would produce greater effects on dopamine (DA) systems than would either compound administered alone. Male C57BL/6 mice were treated twice a week for 6 weeks with intraperitoneal saline, 10 mg/kg paraquat, 30 mg/kg maneb, or their combination (PQ + MB). MB, but not PQ, reduced motor activity immediately after treatment, and this effect was potentiated by combined PQ + MB treatment. As treatments progressed, only the combined PQ + MB group evidenced a failure of motor activity levels to recover within 24 hr. Striatal DA and dihydroxyphenylacetic acid increased 1-3 d and decreased 7 d after injections. Only PQ + MB reduced tyrosine hydroxylase (TH) and DA transporter immunoreactivity and did so in dorsal striatum but not nucleus accumbens. Correspondingly, striatal TH protein levels were decreased only by combined PQ + MB 5 d after injection. Reactive gliosis occurred only in response to combined PQ + MB in dorsal-medial but not ventral striatum. TH immunoreactivity and cell counts were reduced only by PQ + MB and in the substantia nigra but not ventral tegmental area. These synergistic effects of combined PQ + MB, preferentially expressed in the nigrostriatal DA system, suggest that such mixtures could play a role in the etiology of PD.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Body Weight; Carrier Proteins; Cell Count; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Drug Administration Schedule; Drug Synergism; Glial Fibrillary Acidic Protein; Gliosis; Injections, Intraperitoneal; Lung; Male; Maneb; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Motor Activity; Nerve Tissue Proteins; Nucleus Accumbens; Paraquat; Parkinson Disease, Secondary; Substantia Nigra; Tyrosine 3-Monooxygenase; Ventral Tegmental Area

Permanent parkinsonism was observed in a man with chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate). Symptoms developed at 37 years of age, two years after exposure had ceased. To our knowledge, this is the second report on parkinsonism associated with exposure to maneb. Manganese is a well-known parkinsonigen toxin in humans. More recently, it has been shown that dithiocarbamates can also induce extrapyramidal syndromes. The biochemical effects of manganese and dithiocarbamates are reviewed and their possible neurotoxic mechanisms are discussed. Both of these components may have played a role in this case.

Topics: Humans; Male; Maneb; Manganese; Middle Aged; Occupational Exposure; Parkinson Disease, Secondary