RESUMO
Manganese (Mn) is an essential element. However, Mn overexposure is associated with motor dysfunction. This cross-sectional study assessed the association between bone Mn (BnMn) and whole blood Mn (BMn) with motor function in 59 Chinese workers. BnMn and BMn were measured using a transportable in vivo neutron activation analysis system and inductively coupled plasma mass spectrometry, respectively. Motor function (manual coordination, postural sway, postural hand tremor, and fine motor function) was assessed using the Coordination Ability Test System (CATSYS) and the Purdue Pegboard. Relationships between Mn biomarkers and motor test scores were analyzed with linear regression models adjusted for age, education, current employment, and current alcohol consumption. BMn was significantly inversely associated with hand tremor intensity (dominant hand (ß=-0.04, 95 % confidence interval (CI):-0.07, -0.01; non-dominant hand ß=-0.05, 95 % CI:-0.08, -0.01) hand tremor center frequency (non-dominant hand ß=-1.61, 95 % CI:-3.03, -0.19) and positively associated with the Purdue Pegboard Assembly Score (ß = 4.58, 95 % CI:1.08, 8.07). BnMn was significantly inversely associated with finger-tapping performance (non-dominant hand ß=-0.02, 95 % CI:-0.04,-0.004), mean sway (eyes closed and foam ß=-0.68, 95 % CI:-1.31,-0.04), and positively associated with hand tremor center frequency (dominant hand, ß = 0.40, 95 % CI:0.002, 0.80). These results suggest BMn is related to better postural hand tremor and fine motor control and BnMn is related to worse motor coordination and postural hand tremor but better (i.e., less) postural sway. The unexpected positive results might be explained by choice of biomarker or confounding by work-related motor activities. Larger, longitudinal studies in this area are recommended.
Assuntos
Osso e Ossos/química , Manganês/análise , Destreza Motora/efeitos dos fármacos , Adulto , China , Estudos Transversais , Humanos , Masculino , Manganês/sangue , Intoxicação por Manganês/sangue , Intoxicação por Manganês/complicações , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Tremor/induzido quimicamenteRESUMO
Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function. They also play vital roles in the central nervous system as significant cofactors for several enzymes, including the antioxidant enzyme superoxide dismutase (SOD) and other enzymes that take part in the creation and breakdown of neurotransmitters in the brain. An imbalance in the levels of these metals weakens the structural, regulatory, and catalytic roles of different enzymes, proteins, receptors, and transporters and is known to provoke the development of various neurological conditions through different mechanisms, such as via induction of oxidative stress, increased α-synuclein aggregation and fibril formation, and stimulation of microglial cells, thus resulting in inflammation and reduced production of metalloproteins. In the present review, the authors focus on neurological disorders with psychiatric signs associated with copper, iron, and manganese excess and the diagnosis and potential treatment of such disorders. In our review, we described diseases related to these metals, such as aceruloplasminaemia, neuroferritinopathy, pantothenate kinase-associated neurodegeneration (PKAN) and other very rare classical NBIA forms, manganism, attention-deficit/hyperactivity disorder (ADHD), ephedrone encephalopathy, HMNDYT1-SLC30A10 deficiency (HMNDYT1), HMNDYT2-SLC39A14 deficiency, CDG2N-SLC39A8 deficiency, hepatic encephalopathy, prion disease and "prion-like disease", amyotrophic lateral sclerosis, Huntington's disease, Friedreich's ataxia, and depression.
Assuntos
Ceruloplasmina/deficiência , Cobre/efeitos adversos , Distúrbios do Metabolismo do Ferro/patologia , Ferro/efeitos adversos , Manganês/efeitos adversos , Doenças Metabólicas/patologia , Distrofias Neuroaxonais/patologia , Doenças Neurodegenerativas/patologia , Humanos , Distúrbios do Metabolismo do Ferro/induzido quimicamente , Distúrbios do Metabolismo do Ferro/etiologia , Intoxicação por Manganês/complicações , Doenças Metabólicas/induzido quimicamente , Metaloproteínas/metabolismo , Distrofias Neuroaxonais/induzido quimicamente , Doenças Neurodegenerativas/etiologia , Estresse OxidativoRESUMO
Manganese (Mn) is an essential element, however, children with moderate to high Mn exposure can exhibit neurobehavioral impairments. One way Mn appears to affect brain function is through altering dopaminergic systems involved with motor and cognitive control including frontal - striatal brain systems. Based on the risk for motor and attention problems, we evaluated neurobehavioral function in 255 children at risk for Mn exposure due to living in proximity to coal ash storage sites. Proton Induced X-ray Emissions (PIXE) analysis was conducted on finger and toenails samples. Multiple neuropsychological tests were completed with the children. Fifty-five children had Mn concentrations above the limit of detection (LOD) (median concentration = 3.95 ppm). Children with detectable Mn concentrations had reduced visual motor skills (ß = -5.62, CI: -9.11, -2.12, p = 0.008) and more problems with sustained attention, based on incorrect responses on a computerized attention test, (ß = 0.40, CI: 0.21, 0.59, p < 0.001) compared with children who had Mn concentrations below the LOD. Findings suggest that Mn exposure impacts attention and motor control possibly due to neurotoxicity involving basal ganglia and forebrain regions. Visual-motor and attention tests may provide a sensitive measure of Mn neurotoxicity, useful for evaluating the effects of exposure in children and leading to better treatment options.
Assuntos
Atenção/fisiologia , Carga Corporal (Radioterapia) , Exposição Ambiental/efeitos adversos , Manganês/toxicidade , Síndromes Neurotóxicas/etiologia , Atenção/efeitos dos fármacos , Criança , Feminino , Humanos , Masculino , Intoxicação por Manganês/complicações , Destreza Motora/efeitos dos fármacos , Testes NeuropsicológicosRESUMO
The aim of this study was to evaluate the effect of exposure to manganese (Mn) on fine motor functions. A total of 48 welders and 30 unexposed workers as controls completed questionnaires, underwent blood examinations, and a motor test battery. The shift exposure of welders to respirable Mn was measured with personal samplers. For all subjects accumulations of Mn in the brain were assessed with T1-weighted magnetic resonance imaging. Welders showed normal motor functions on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale part III. Furthermore welders performed excellent on a steadiness test, showing better results than controls. However, welders were slightly slower than controls in motor tests. There was no association between fine motor test results and the relaxation rates R1 in globus pallidus and substantia nigra as MRI-based biomarkers to quantify Mn deposition in the brain.
Assuntos
Encéfalo/efeitos dos fármacos , Intoxicação por Manganês/complicações , Ferreiros , Destreza Motora/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética , Manganês/toxicidade , Pessoa de Meia-Idade , Neuroimagem , Exposição Ocupacional/estatística & dados numéricosRESUMO
AIM: The study presents neuropsychological characteristic of 16 individuals with manganese-induced parkinsonism due to intravenous ephedrone use. MATERIAL AND METHODS: Overall cognitive function screening as well as full examination of various cognitive domains (verbal learning, visual memory, working memory, executive functions, construction and visuospatial functions) with the use of elastic neuropsychological test battery were performed. Dyshartric speech disorders were also precisely evaluated. Additionally, all individuals filled in the Beck Depression Inventory (BDI), which is used to assess mood. RESULTS: All patients had evident dysarthric speech disorders accompanied with palilalia and writing disorders (micrographia) in the majority of investigated individuals. Neuropsychological screening diagnosis showed no overall cognitive deficits at the level of dementia. Mild decrease in verbal learning and visual memory processes was found; as well as ideomotor but no construction praxis disorders. Results of working memory and executive function assessment indicated decrease in cognitive flexibility and logical conceptualization abilities, as well as set-shifting disorders. Patients varied significantly in their severity of executive dysfunction. Duration of ephedrone use was found nonsignificant for patients' cognition. The mean BDI score indicated moderate depression. Higher level of depressive symptoms was associated with poorer overall cognitive screening, decrease of visual and verbal learning as well as phonemic verbal fluency.
Assuntos
Encefalopatias/induzido quimicamente , Transtornos Cognitivos/induzido quimicamente , Intoxicação por Manganês/complicações , Propiofenonas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/etiologia , Adulto , Encefalopatias/diagnóstico , Transtornos Cognitivos/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Excessive levels of the essential metal manganese (Mn) may cause a syndrome similar to Parkinson's disease. The model organism Caenorhabditis elegans mimics some of Mn effects in mammals, including dopaminergic neurodegeneration, oxidative stress, and increased levels of AKT. The evolutionarily conserved insulin/insulin-like growth factor-1 signaling pathway (IIS) modulates worm longevity, metabolism, and antioxidant responses by antagonizing the transcription factors DAF-16/FOXO and SKN-1/Nrf-2. AKT-1, AKT-2, and SGK-1 act upstream of these transcription factors. To study the role of these proteins in C. elegans response to Mn intoxication, wild-type N2 and loss-of-function mutants were exposed to Mn (2.5 to 100 mM) for 1 h at the L1 larval stage. Strains with loss-of-function in akt-1, akt-2, and sgk-1 had higher resistance to Mn compared to N2 in the survival test. All strains tested accumulated Mn similarly, as shown by ICP-MS. DAF-16 nuclear translocation was observed by fluorescence microscopy in WT and loss-of-function strains exposed to Mn. qRT-PCR data indicate increased expression of γ-glutamyl cysteine synthetase (GCS-1) antioxidant enzyme in akt-1 mutants. The expression of sod-3 (superoxide dismutase homologue) was increased in the akt-1 mutant worms, independent of Mn treatment. However, dopaminergic neurons degenerated even in the more resistant strains. Dopaminergic function was evaluated with the basal slowing response behavioral test and dopaminergic neuron integrity was evaluated using worms expressing green fluorescent protein (GFP) under the dopamine transporter (DAT-1) promoter. These results suggest that AKT-1/2 and SGK-1 play a role in C. elegans response to Mn intoxication. However, tissue-specific responses may occur in dopaminergic neurons, contributing to degeneration.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Cloretos/toxicidade , Intoxicação por Manganês/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/genética , Animais , Animais Geneticamente Modificados , Comportamento Animal/fisiologia , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Modelos Animais de Doenças , Dopamina/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Glutationa/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Compostos de Manganês , Intoxicação por Manganês/complicações , Intoxicação por Manganês/patologia , Mutação/genética , Degeneração Neural/etiologia , Degeneração Neural/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
Methcathinone-induced Parkinsonism is a recently described extrapyramidal syndrome characterized by globus pallidus and substantia nigra lesions, which provides a unique model of basal ganglia dysfunction. We assessed motivated behaviour in this condition using a novel cost-benefit decision-making task, in which participants decided whether it was worth investing effort for reward. Patients showed a dissociation between reward and effort sensitivity, such that pallidonigral complex dysfunction caused them to become less sensitive to rewards, while normal sensitivity to effort costs was maintained.
Assuntos
Intoxicação por Manganês/complicações , Motivação/fisiologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/psicologia , Propiofenonas/efeitos adversos , Recompensa , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Estudos de Casos e Controles , Tomada de Decisões/fisiologia , Feminino , Humanos , Masculino , Motivação/efeitos dos fármacos , Doença de Parkinson Secundária/diagnóstico por imagemRESUMO
Although an essential nutrient, manganese (Mn) can be toxic at high doses. There is, however, uncertainty regarding the effects of chronic low-level Mn-exposure. This review provides an overview of Mn-related brain and functional changes based on studies of a cohort of asymptomatic welders who had lower Mn-exposure than in most previous work. In welders with low-level Mn-exposure, we found: 1) Mn may accumulate in the brain in a non-linear fashion: MRI R1 (1/T1) signals significantly increased only after a critical level of exposure was reached (e.g., ≥300 welding hours in the past 90days prior to MRI). Moreover, R1 may be a more sensitive marker to capture short-term dynamic changes in Mn accumulation than the pallidal index [T1-weighted intensity ratio of the globus pallidus vs. frontal white matter], a traditional marker for Mn accumulation; 2) Chronic Mn-exposure may lead to microstructural changes as indicated by lower diffusion tensor fractional anisotropy values in the basal ganglia (BG), especially when welding years exceeded more than 30 years; 3) Mn-related subtle motor dysfunctions can be captured sensitively by synergy metrics (indices for movement stability), whereas traditional fine motor tasks failed to detect any significant differences; and 4) Iron (Fe) also may play a role in welding-related neurotoxicity, especially at low-level Mn-exposure, evidenced by higher R2* values (an estimate for brain Fe accumulation) in the BG. Moreover, higher R2* values were associated with lower phonemic fluency performance. These findings may guide future studies and the development of occupation- and public health-related polices involving Mn-exposure.
Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Intoxicação por Manganês/patologia , Intoxicação por Manganês/fisiopatologia , Exposição Ocupacional , Soldagem , Adulto , Humanos , Ferro/metabolismo , Masculino , Manganês/metabolismo , Intoxicação por Manganês/complicações , Pessoa de Meia-Idade , Transtornos Motores/induzido quimicamenteRESUMO
BACKGROUND: This study investigated the validity of self-reported concentration and memory problems (CMP) in residents environmentally exposed to manganese (Mn). METHOD: Self-report of CMP from a health questionnaire (HQ) and the Symptom Checklist-90-Revised (SCL-90-R) was compared to neuropsychological assessment (Trails A&B; Digit Span; Digit Symbol; Similarities; Auditory Consonant Trigrams, ACT; NAB Memory; Rey-Osterrieth, Rey-O, Delayed). Participants included 146 residents from Ohio exposed to air-Mn, with a modeled average concentration of 0.55 µg m-3 (range = 0.01-4.58). RESULTS: Residents were primarily White (94.5%), aged 30-64 years (M = 51.24), with a minimum of 10 years of residence (range = 10-64). Ninety-four (65.3%) participants reported concentration problems, and 107 residents (73.3%) reported memory problems. More participants endorsed CMP on the SCL-90-R than on the HQ. The prevalence of self-reported CMP was higher for women than for men (88.4% vs. 68.3%). Point-biserial and Pearson's correlations between self-reported CMP and neuropsychological test scores were nonsignificant and weak for both the HQ (rpb = -.20 to rpb = .04) and the SCL-90-R (r = -.12 to r = .007). Greater levels of depression, anxiety, and female sex predicted having more self-reported CMP on both the HQ and the SCL-90-R. Air-Mn and blood-Mn were not associated with self-reported CMP. Residential distance from the Mn source accounted for a small proportion of variance (sr2 = .04), although depression remained the largest predictor (sr2 = .21). CONCLUSION: These results indicate that self-report of CMP in Mn-exposed residents appear to be invalid when compared to neuropsychological test scores. The participants' misperception of having CMP is associated with less education and higher levels of depression. Neuropsychological assessment is recommended to attain valid results.
Assuntos
Disfunção Cognitiva/induzido quimicamente , Autoavaliação Diagnóstica , Intoxicação por Manganês/complicações , Transtornos da Memória/induzido quimicamente , Testes Neuropsicológicos , Autorrelato/normas , Adulto , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: In the last fifteen years a new cause of chronic manganese toxicity has been recognized. It follows recreational intravenous injections of Ephedrone, synthesized from a cold remedies contained pseudoephedrine. Potassium permanganate is used as an oxidant. It presents with severe parkinsonism-dystonia and a characteristic dysarthria. OBJECTIVES: We performed a focus perceptual study of dysarthria in Ephedrone induced parkinsonism and compared the findings with the speech disorders seen in Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS: A digital voice recording, perceptual speech analysis (Darley, 1975) [18], serial neurological assessment and Brain Magnetic Resonance (MR) imaging were performed at the Lviv regional Clinical Hospital. The results were analysed at the Institute of Neurology in London. RESULTS: Dysarthria developed after 8.5±3.2months of daily intravenous Ephedrone abuse and was an initial symptom in a third of cases. It was characterised by a robotic-flat prosody, whispering or continuous phonation, an inability to regulate pitch and volume, frozen lip articulation, a variable degree of dystonic tightness, difficulties in speech initiation and palladia, There was no nasality and swallowing was normal. In some patients speech deteriorated even after the discontinuation of Ephedrone. MR imaging, performed soon after drug cessation showed T1 signal hyperintesity in striatum and pallidum, especially in the Globus Pallidum interna. CONCLUSION: Ephedrone induced chronic manganese toxicity can lead to a mixed hypokinetic-dystonic dysarthria with a distinct dystonic pattern. Perceptual speech analysis can be a helpful ancillary investigation in the differential diagnosis of parkinsonism, and may permit the recognition of chronic manganese toxicity.
Assuntos
Disartria/etiologia , Globo Pálido/diagnóstico por imagem , Intoxicação por Manganês/complicações , Neostriado/diagnóstico por imagem , Doença de Parkinson Secundária/complicações , Propiofenonas/toxicidade , Adulto , Disartria/induzido quimicamente , Humanos , Masculino , Intoxicação por Manganês/etiologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/diagnóstico por imagemRESUMO
This paper describes two patients who were exposed to toxic substances in the workplace, but for whom diagnosis proved difficult, particularly in case 2. Case 1 was exposed to methyl iodide and case 2 to manganese. Poisoning was characterised by delayed onset of symptoms following exposure and symptom progression after cessation of exposure. The clinical consequences of exposure to these substances include cerebellar and Parkinsonian symptoms followed by the development of cognitive impairment and the late appearance of psychiatric disturbances. Both cases were evaluated by physicians with little training in toxicology. Apart from abnormal liver function in case 1 and decreased power, coordination and proprioception in case 2, results of most routine medical investigations were normal. Both cases were referred for MRI brain scan and neuropsychological assessment. Abnormalities were noted on MRI but reported as being absent initially in case 1and of unknown significance in case 2. There was evidence of cognitive impairment in both and personality change in case 1 of sufficient severity to prevent both cases from returning to work and to impact on family life. There is no antidote to methyl iodide or manganese poisoning. Successful treatment requires early diagnosis and cessation of exposure, but neurotoxic syndromes are difficult to diagnose when a time lag exists between exposure and symptom onset and there is no biomarker of exposure. These syndromes may initially be confused with other neurodegenerative conditions, infectious processes, and psychiatric disorders. Clinician's lack of familiarity with the potential toxicity of environmental and industrial chemicals can lead to misdiagnosis and mismanagement, and this lack of recognition can lead to continued exposure. These cases highlight the importance of taking a detailed occupational history in patients who present with atypical neurological symptoms.
Assuntos
Transtornos Cognitivos/induzido quimicamente , Hidrocarbonetos Iodados/intoxicação , Intoxicação por Manganês/complicações , Exposição Ocupacional/efeitos adversos , Doença de Parkinson Secundária/induzido quimicamente , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Erros de Diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/psicologia , Fatores de TempoRESUMO
Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson's disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson's disease (PD).
Assuntos
Intoxicação por Manganês/complicações , Intoxicação por Manganês/fisiopatologia , Doença de Parkinson/fisiopatologia , Transtornos Parkinsonianos/induzido quimicamente , Encéfalo , Dopamina , Ácido Glutâmico , Humanos , Magnésio/farmacocinética , Ácido gama-AminobutíricoRESUMO
Intravenous injection of self-produced ephedrone (metcathinone) using potassium permanganate as an oxidant can lead to severe, fixed encephalopathy. This risk applies mainly to young individuals experimenting with "home-made" drugs and results in an irreversible aggravation of overall functioning. Besides multiple neurological symptoms and movement disorders, affected individuals also experience cognitive dysfunction. No systematic research has been conducted in this field. Single case reports and small group descriptions show that assessment with screening tools such as the Mini-Mental State Examination (MMSE) is ineffective. Neuropsychological assessment conducted with other tests indicates significant dysarthric speech disorders, psychomotor function impairment, attentional disorders of varying intensity as well as dysfunctions of verbal and visual working memory processes. Some studies of this group of subjects also indicate working memory and executive function disorders. These dysfunctions seem to be permanent and do not recede following manganese use discontinuation and an improvement of the neuroradiological picture in MRI assessment. A standard test battery should be developed enabling the assessment of both cognitive and neurological dysfunctions that otherwise render some tests impossible to administer.
Assuntos
Encefalopatia Hipertensiva/induzido quimicamente , Drogas Ilícitas/intoxicação , Intoxicação por Manganês/complicações , Propiofenonas/intoxicação , Abuso de Substâncias por Via Intravenosa/complicações , Humanos , Intoxicação por Manganês/diagnóstico , Testes Neuropsicológicos , Propiofenonas/administração & dosagem , Assunção de Riscos , Abuso de Substâncias por Via Intravenosa/diagnósticoRESUMO
INTRODUCTION: In occupational epidemiologic studies, the low incidence and chronic process of central nervous system (CNS) diseases has complicated the determination of the relationship between increased morbidity and manganese (Mn) exposure. Therefore, through this large cohort study, we evaluated CNS disease morbidity among Korean workers exposed to Mn METHODS: Data were collected from Mn-associated specialized medical check-up 2000 and 2004 in Korea. The number of workers admitted to hospital because of clinically diagnosed CNS disease was analyzed in male workers exposed to Mn (n = 104,544). As a control reference population, 2% of Korean men were randomly selected and their hospital admission data were analyzed. For Mn-exposed workers, Standardized admission ratios (SARs) for CNS disease, as determined by ICD-10 classifications, were estimated in reference to the control population RESULTS: During follow up, 64 workers admitted because of CNS diseases. Chronic exposure to Mn (≥ 10 years) was significantly associated with the SAR (95% CI) of extrapyramidal and movement disorders (SAR: 2.03, 95% CI: 1.05-3.55), in particular, other extrapyramidal and movement disorders (SAR: 4.81, 95% CI: 1.29-12.32). Also borderline association (SAR = 4.88, 90% CI: 1.05-7.04) was noted for secondary Parkinsonism among workers with chronic Mn exposure. SARs (95% CI) for other degenerative nervous system diseases were significantly higher in Mn-exposed workers compared with the control population (SAR: 3.60, 95% CI: 1.16-8.40) CONCLUSION: In conclusion, Mn-exposed workers exhibited significantly elevated SARs for degenerative nervous system diseases and extrapyramidal and movement disorders, compared to the age-matched reference population, suggesting a relatedness with Mn exposure.
Assuntos
Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/etiologia , Intoxicação por Manganês/complicações , Intoxicação por Manganês/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Adulto , Distribuição por Idade , Feminino , Inquéritos Epidemiológicos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/epidemiologia , Transtornos dos Movimentos/etiologia , República da Coreia/epidemiologia , Adulto JovemRESUMO
The pathological role of α-synuclein (α-Syn) aggregation in neurodegeneration is well recognized, but the physiological function of normal α-Syn remains unknown. As α-Syn protein contains multiple divalent metal binding sites, herein we conducted a comprehensive characterization of the role of α-Syn in manganese-induced dopaminergic neurotoxicity. We established transgenic N27 dopaminergic neuronal cells by stably expressing human wild-type α-Syn at normal physiological levels. α-Syn-expressing dopaminergic cells significantly attenuated Mn-induced neurotoxicity for 24-h exposures relative to vector control cells. To further explore cellular mechanisms, we studied the mitochondria-dependent apoptotic pathway. Analysis of a key mitochondrial apoptotic initiator, cytochrome c, revealed that α-Syn significantly reduces the Mn-induced cytochrome c release into cytosol. The downstream caspase cascade, involving caspase-9 and caspase-3 activation, during Mn exposure was also largely attenuated in Mn-treated α-Syn cells in a time-dependent manner. α-Syn cells also showed a dramatic reduction in the Mn-induced proteolytic activation of the pro-apoptotic kinase PKCδ. The generation of Mn-induced reactive oxygen species (ROS) did not differ between α-Syn and vector control cells, indicating that α-Syn exerts its protective effect independent of altering ROS generation. Inductively coupled plasma-mass spectrometry (ICP-MS) revealed no significant differences in intracellular Mn levels between treated vector and α-Syn cells. Notably, the expression of wild-type α-Syn in primary mesencephalic cells also rescued cells from Mn-induced neurotoxicity. However, prolonged exposure to Mn promoted protein aggregation in α-Syn-expressing cells. Collectively, these results demonstrate that wild-type α-Syn exhibits neuroprotective effects against Mn-induced neurotoxicity during the early stages of exposure in a dopaminergic neuronal model of PD.
Assuntos
Cloretos/toxicidade , Neurônios Dopaminérgicos/efeitos dos fármacos , Intoxicação por Manganês/genética , Modelos Neurológicos , Doença de Parkinson/genética , alfa-Sinucleína/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Sítios de Ligação , Western Blotting , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Cloretos/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Humanos , Compostos de Manganês/metabolismo , Intoxicação por Manganês/complicações , Intoxicação por Manganês/patologia , Intoxicação por Manganês/prevenção & controle , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Mesencéfalo/patologia , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Doença de Parkinson/prevenção & controle , Ligação Proteica , Ratos , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Atômica , Transfecção , alfa-Sinucleína/metabolismoRESUMO
Manganese (Mn) toxicity causes an extrapyramidal, parkinsonian-type movement disorder with characteristic magnetic resonance images of Mn accumulation in the basal ganglia. This letter highlights the neurological manifestations and neuroimaging features of inherited manganism (IMn), an unusual and treatable inborn error of Mn homeostasis. Early-onset dystonia with "cock-walk" gait and hyperintense signal in basal ganglia, associated to polycythemia, chronic liver disease and hypermanganesemia, promptly suggest IMn, and a genetic evaluation should be performed.
Assuntos
Transtornos Neurológicos da Marcha , Intoxicação por Manganês , Neuroimagem , Proteínas de Transporte de Cátions/genética , Criança , Feminino , Transtornos Neurológicos da Marcha/complicações , Transtornos Neurológicos da Marcha/genética , Transtornos Neurológicos da Marcha/patologia , Humanos , Intoxicação por Manganês/complicações , Intoxicação por Manganês/genética , Intoxicação por Manganês/patologia , Transportador 8 de ZincoRESUMO
AIM: In this study, cognitive functions of 9 patients developing parkinsonism due to chronic manganese intoxication by intravenous methcathinone solution were investigated using detailed neuropsychometric tests. METHOD: Attention deficit, verbal and nonverbal memory, visuospatial function, constructive ability, language, and executive (frontal) functions of 9 patients who were admitted to our clinic with manifestations of chronic manganese intoxication and 9 control subjects were assessed using neuropsychometric tests. Two years later, detailed repeat neuropsychometric tests were performed in the patient group. The results were evaluated using the χ(2) test, Fisher's exact probability test, Student's t test and the Mann-Whitney U test. RESULTS: While there was no statistically significant difference between the two groups in language functions, visuospatial functions and constructive ability, a statistically significant difference was noted between both groups regarding attention (p = 0.032), calculation (p = 0.004), recall and recognition domains of verbal memory, nonverbal memory (p = 0.021) and some domains of frontal functions (Stroop-5 and spontaneous recovery) (p = 0.022 and 0.012). Repeat neuropsychometric test results of the patients were not statistically significant 2 years later. CONCLUSION: It has been observed that cognitive dysfunction seen in parkinsonism secondary to chronic manganese intoxication may be long-lasting and may not recover as observed in motor dysfunction.
Assuntos
Transtornos Cognitivos/induzido quimicamente , Intoxicação por Manganês/complicações , Transtornos Parkinsonianos/induzido quimicamente , Propiofenonas/intoxicação , Psicotrópicos/intoxicação , Adulto , Humanos , Masculino , Testes Neuropsicológicos , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto JovemRESUMO
Airborne manganese (Mn) exposure can result in neurotoxicity and postural instability in occupationally exposed workers, yet few studies have explored the association ambient exposure to Mn in children and postural stability. The goal of this study was to determine the association between Mn and lead (Pb) exposure, as measured by blood Pb, blood and hair Mn and time weighted distance (TWD) from a ferromanganese refinery, and postural stability in children. A subset of children ages 7-9 years enrolled in the Marietta Community Actively Researching Exposure Study (CARES) were invited to participate. Postural balance was conducted on 55 children residing in Marietta, Ohio and the surrounding area. Samples of blood were collected and analyzed for Mn and Pb, and samples of hair were analyzed for Mn. Neuromotor performance was assessed using postural balance testing with a computer force platform system. Pearson correlations were calculated to identify key covariates. Associations between postural balance testing conditions and Mn and Pb exposure were estimated with linear regression analyses adjusting for gender, age, parent IQ, and parent age. Mean blood Mn was 10 µg/L (SEM=0.36), mean blood Pb was 0.85 µg/dL (SEM=0.05), and mean hair Mn was 0.76 µg/g (SEM=0.16). Mean residential distance from the refinery was 11.5 km (SEM=0.46). All three measures of Mn exposure were significantly associated with poor postural balance. In addition, low-level blood Pb was also negatively associated with balance outcomes. We conclude that Mn exposure and low-level blood Pb are significantly associated with poor postural balance.
Assuntos
Exposição Ambiental , Ferro/toxicidade , Intoxicação por Manganês/complicações , Manganês/toxicidade , Equilíbrio Postural/efeitos dos fármacos , Transtornos de Sensação/induzido quimicamente , Fatores Etários , Criança , Meio Ambiente , Feminino , Humanos , Inteligência , Ferro/sangue , Masculino , Manganês/sangue , Intoxicação por Manganês/etiologia , Ohio , Transtornos de Sensação/sangue , Espectrofotometria AtômicaRESUMO
The iatrogenic risks associated with excessive Mn administration in parenteral nutrition (PN) patients are well documented. Hypermanganesemia and neurotoxicity are associated with the duration of Mn supplementation, Mn dosage, as well as pathological conditions, such as anemia or cholestasis. Recent PN guidelines recommend the biomonitoring of patients if they receive Mn in their PN longer than 30 days. The data in the literature are conflicting about the method for assessing Mn stores in humans as a definitive biomarker of Mn exposure or induced-neurotoxicity has yet to be identified. The biomonitoring of Mn relies on the analysis of whole blood Mn (WB Mn) levels, which are highly variable among human population and are not strictly correlated with Mn-induced neurotoxicity. Alterations in dopaminergic (DAergic) and catecholaminergic metabolism have been studied as predictive biomarkers of Mn-induced neurotoxicity. Given these limitations, this review addresses various approaches for biomonitoring Mn exposure and neurotoxic risk.
Assuntos
Monitoramento Ambiental , Intoxicação por Manganês/complicações , Manganês/administração & dosagem , Síndromes Neurotóxicas/etiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Feminino , Humanos , Masculino , GravidezRESUMO
Neurobehavioral functions were studied in 137 welders exposed to the geometric mean (GM) air concentration of 214 µg/m(3) (range 1-3230) of manganese (Mn) based on the individual mean from two days of air sampling. Only 22 µg/m(3) (GM) was soluble in the artificial lung fluid Hatch solution. The welders were compared to 137 referents (turner/fitters) recruited from the same plants. The GM concentrations of Mn in whole blood (B-Mn) and urine (U-Mn) were 12.8 µg/L and 0.36 µg/g creatinine versus 8.0 µg/L and 0.07 µg/g creatinine in the referents. Alcohol consumption was assessed by measuring carbohydrate deficient transferrin in serum (sCDT). The welders had poorer performance than the referents on the Grooved Pegboard, Finger Tapping, Simple Reaction Time (SRT) and possibly the Maximum Frequency tests. They also reported more subjective symptoms. Welders with sCDT above the upper reference limit had substantially poorer performances on the Grooved Pegboard test, Finger Tapping test and SRT than welders with sCDT below this level. No effect of high sCDT was observed in the referents, indicating an interaction between high sCDT and exposure to Mn for these tests. Self-reported alcohol consumption had no impact on these neurobehavioral test results. A statistically significant difference in the SRT and Grooved Pegboard test results remained after excluding all subjects with sCDT above the normal level, but the difference in test scores between the groups was smaller. These welders also reported more subjective symptoms than the referents. The results suggest that sCDT should be measured in neurobehavioral studies of occupationally Mn exposed populations for a more precise estimation of high alcohol consumption.