Curcumin alleviates the manganese-induced neurotoxicity by promoting autophagy in rat models of manganism / 北京大学学报(医学版)

OBJECTIVE@#To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl2), which mimics mangnism.@*METHODS@#Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H2O intragastrically (ig), MnCl2 group received 15 mg/kg MnCl2(Mn2+ 6.48 mg/kg) intraperitoneally plus dd H2O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl2+ CUR1 group received 15 mg/kg MnCl2 intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl2+ CUR2 group received 15 mg/kg MnCl2 intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum.@*RESULTS@#After exposure to MnCl2 for four weeks, MnCl2-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH+ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl2 group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl2 group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl2 group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl2+ CUR2 group were significantly improved compared with MnCl2 group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl2+ CUR2 group compared with MnCl2 group. Further, compared with MnCl2 group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl2+ CUR2 group (P < 0.05).@*CONCLUSION@#Curcumin alleviated the MnCl2-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.

Evaluación toxicológica y de metales (Cu, Pb, Ni, Zn y Cd) en el sedimento del reservorio Paiva Castro en Mairiporã-SP, Brasil / Toxicological and metal evaluation (Cu, Pb, Ni, Zn and Cd) in the sediment of Paiva Castro reservoir, in Mairiporã-SP, Brasil

El hombre ha cambiado el ambiente para sostener la demanda global de recursos naturales como el agua. La gestión de los cuerpos hídricos tiene que ser constante, con el propósito preventivo y correctivo, dependiendo del estado de antropización de cada sistema. El objetivo de este artículo fue analizar la toxicidad del sedimento y los metales Mn, Zn, Pb, Ni, Cd y Cu, en el reservorio Paiva Castro, que abastece la Region Metropolitana de São Paulo. Se realizaron 2 muestreos (Mayo 2011, estación seca y Enero de 2012, estación húmeda) y se analizaron 5 puntos próximos a la captación de agua por la Companhia de Saneamento Básico do Estado de São Paulo. Se realizaron ensayos de toxicidad aguda y crónica en sedimento, a través de ensayos biológicos con el cladócero Daphnia similis y el insecto Chironomus xanthus. El tratamiento de datos se realizó con el test de Fisher (mortalidad). El nivel de asociación entre las variables en sedimento y en los test ecotoxicológicos fueron evaluados por test no-paramétricos, a través del coeficiente de correlación de Spearman's. Los resultados del presente trabajo señalaron bajas concentracones de metales en el sedimento del área de estudio y ausencia de toxicidad en los organismos ensayados. Se puede concluir que área estudiada del reservorio Paiva Castro se encuentra poco impactada por los metales, sin efectos directos sobre la calidad de vida los organismos bentónicos: D. similis y C. xanthus.

Man had changed the natural environment in an attempt trying to supply the global demand for resources. The management of the hydric bodies has to be constant, with preventive and corrective purpose, depending on the eutrophization state of each one. The objective of this article was to analyze the sediment toxicity and the metals Mn, Zn, Pb, Ni, Cd and Cu, in the Paiva Castro reservoir, that supply the Metropolitan Region of São Paulo. It was made 2 collections (May 2011, dry season and January 2012, wet season). It was analyzed 5 points next to the water captation station by the Companhia de Saneamento Básico do Estado de São Paulo. The sediment was analyzed as for acute and chronic toxicity through bioassays with the cladocerans Daphnia similis and the insect Chironomus xanthus. Data treatment was done with Fisher Exact Test (mortality). The association level between the variables in sediment and ecotoxicological tests was available in non-parametric tests, through the Spearman's correlation coefficient. Oriented on the results presented in this work, pointing low concentrations of heavy metals in the sediments presented in the collect local, and the absence of toxicity, we can say that at this reservoir, at least in the collect area, it's low impacted, not implicating in direct interferences in the quality of life of benthonic organisms.

Níveis de metais no solo e na água da microbacia do distrito Industrial do Pequiá, município de Açailândia, MA / Levels of metals in soil and water catchment Industrial District Pequiá, municipality of Açailândia, MA

Este estudo determinou a concentração de vários metais no solo e na água da microbacia do distrito industrial do Pequiá, Açailândia-MA, e investigou a variação das concentrações dos metais no solo em função da distância às indústrias. Os metais investigados os metais foram Arsênio (As), Cádmio (Cd), Manganês (Mn), Mercúrio (Hg), Chumbo (Pb) e Níquel (Ni), que podem acarretar diversos agravos na saúde em virtude da sua toxicidade em diferentes alvos biológicos. O distrito industrial do Pequiá é caracterizado por indústrias siderúrgicas e rodovias com intenso tráfego de veículos a combustão, o que desperta a necessidade de se conhecer as concentrações ambientais desses metais. Metodologia: Foram coletadas 44 amostras de solo do entorno das indústrias nos período seco e chuvoso, respectivamente, e água de três pontos do córrego Pequiá no período chuvoso. A determinação da concentração de metais em solo foi realizada por Espectrometria de Emissão Atômica por Plasma Acoplado Indutivamente (ICP-OES), e em água por meio de Espectrometria de Massa com Plasma Acoplado Indutivamente (ICP-MS). (...) O único metal detectado em todas as amostras no período seco foi o Hg. A análise de correlação entre as concentrações no solo em cada período revelou correlação positiva estatisticamente significativa entre Pb e Mn no período chuvoso e correlação negativa com significância limítrofe entre Mn e Hg. Em relação ao gradiente de concentração, se observou diminuição apenas da concentração de Pb ao longo da linha reta entre as indústrias e o bairro Pequiá. A diminuição da concentração de Pb com a distância foi estatisticamente significativa, tanto no período chuvoso quanto no seco. Conclusão: Os metais Mn e Pb foram os mais frequentemente encontrados e com as concentrações mais elevadas tanto no solo quanto na água, muito provavelmente devido ao processo de fabricação do ferro gusa e ao intenso tráfego de veículos...

This study determined the concentration of heavy metals in soil and surface water in the industrial district of Pequiá, Açailândia-MA, as well as investigated the variation in concentration of metals in soil with the distance to the industries. Metals investigated were Arsenic (As), Cadmium (Cd), Manganese (Mn), Mercury (Hg), Lead (Pb) and Niquel (Ni), which may cause several health effects. The Pequiá industrial district is composed by several steel plants and roads with heavy vehicle traffic. Methods: Soil samples were collected from 44 points around the industrial district in the dry and rainy season, respectively, and water samples were collected at three points of the Pequiá stream during the rainy season. Concentrations of metals in soil were determined by inductively coupled plasma optical emission spectrometry (ICP-OES), and by inductively coupled plasma mass spectrometry (ICP-MS). (...) Hg was the only metal detected in all soil samples in the dry season. Correlation analysis between concentrations of metals in soil showed a statistically significant positive correlation between Pb e Mn in the rainy season. Pb was the only metal showing a reduction in concentration across the straight line between the industries and Pequiá neighborhood. Reduction in Pb concentration with increasing distance was statistically significant in both seasons. Conclusions: Mn e Pb were the metals most frequently found and those presenting the highest concentrations in soil and water, suggesting that the main sources of these metals in the study area may be iron manufacturing process and motor vehicle traffic...

Avaliação da exposição ambiental ao manganês na população residenteno entorno de um estaleiro no município de Angra dos Reis, RJ / Assessment of environmental exposure to manganese in the resident population in the vicinity of a site in the municipality of Angra dos Reis, RJ

O manganês é um componente essencial no processo de soldagem, porconferir dureza e resistência, assim como na produção do aço, onde é usadocomo agente dessulfurante e redutor. Apesar de ser um elemento essencial ao homem, atuando na formação dos ossos e tecidos, função reprodutiva e metabolismo de carboidratos e lipídios, a exposição crônica ao Mn afeta, principalmente, o sistema nervoso central. Uma vez que solda e aço são essenciais para a construção e reparo de navios, essa indústria torna-se uma importante fonte de exposição ao referido metal. O objetivo deste trabalho foi avaliar a exposição ao manganês na população residente no entorno de um estaleiro em Angra dos Reis-RJ, que foi comparada a um grupo de moradores do município da Serra-ES. A coleta de dados foi realizada através da aplicação de um questionário padronizado fundamentado para o conhecimento das variáveis sócio-econômicas e fatores de risco para a exposição ao metal, resultando em universo amostral de 98 sujeitos e amostras de ar do local exposto. A técnica analítica utilizada para a determinação do manganês nosfluidos biológicos e nos filtros de ar foi a espectrometria de absorção atômica eletrotérmica. (...)

Manganese and Parkinson's disease: a critical review and new findings / Manganês e doença de Parkinson: uma revisão crítica e novas descobertas

The goal of this review was to examine whether chronic Mn exposure produces dopamine neuron degeneration and PD or whether it has a distinct neuropathology and clinical presentation. I reviewed available clinical, neuroimaging, and neuropathological studies in humans and nonhuman primates exposed to Mn or other human conditions that result in elevated brain Mn concentrations. Human and nonhuman primate literature was examined to compare clinical, neuroimaging, and neuropathological changes associated with Mn-induced parkinsonism. Clinical, neuroimaging, and neuropathological evidence was used to examine whether Mn-induced parkinsonism involves degeneration of the nigrostriatal dopaminergic system as is the case in PD. The overwhelming evidence shows that Mn-induced parkinsonism does not involve degeneration of midbrain dopamine neurons and that l-dopa is not an effective therapy. New evidence is presented on a putative mechanism by which Mn may produce movement abnormalities. Confirmation of this hypothesis in humans is essential to make rational decisions about treatment, devise effective therapeutic strategies, and set regulatory guidelines.

O objetivo desta revisão foi examinar se a exposição crônica ao Mn produz degeneração do neurônio pela dopamina e DP ou se é apenas uma apresentação neuropatológica e clínica diferente. Foram revisados estudos clínicos, de neuroimagens e neuropatológicos disponíveis sobre humanos e primatas expostos ao Mn ou outras condições humanas que resultam em concentrações elevadas de Mn no cérebro. Foi examinada a literatura sobre humanos e primatas e comparadas as mudanças clínicas de neuroimagem e neuropatológicas associadas com o "parkinsonimo" induzido por Mn, envolvendo a degeneração do sistema dopaminérgico nigro-estriatal como no caso da DP. as evidências decisivas mostram que o "parkinsonismo" induzido pelo Mn não envolve a degeneração dos neurônios de dopamina do mesencéfalo e que o dopa-1 não é uma terapia eficaz. Novas evidências estão presentes em um mecanismo putativo pelo qual o Mn pode produzir anormalidades de movimento. A confirmação desta hipótese em humanos é essencial para tomar decisões adequadas sobre o tratamento, planejar estratégias terapêuticas eficazes e estabelecer guias regulatórios.

Abordagem inicial no atendimento ambulatorial em distúrbios neurotoxicológicos. Parte I - metais / Initial approach to outpatient treatment of neurotoxicological disorders. Part I – metals

Introdução: A toxicologia é uma ciência que envolve inúmeros sistemas necessitando de uma equipe multiprofissional e interdisciplinar. A indistinção clínica entre as doenças ocupacionais e não ocupacionais dificulta o seu diagnóstico. Nesse contexto, a neurotoxicologia ocupacional e ambiental estuda os distúrbios do sistema nervoso central (SNC) e periférico (SNP) decorrente da intoxicação dos mais variados agentes. Método: Trata-se de revisão atualizada da literatura a partir de pesquisa na base de dados MEDLINE e LILACS. Também utilizou-se livros e documentos publicados em formato eletrônico. Resultados e Discussão: Distúrbios neuromusculares, distúrbios do movimento, doença do neurônio motor, alterações cognitivocomportamentais e neurofisiológicas têm sido relacionados a inúmeros agentes tóxicos nos últimos anos. A proposta deste artigo é revisar os principais distúrbios neurológicos associados à exposição crônica por metais. A fim de facilitar a abordagem inicial no atendimento ambulatorial aos distúrbios neurotoxicológicos foram confeccionadas tabelas descrevendo os principais agentes tóxicos, as fontes de exposição envolvidas e suasprincipais manifestações neurológicas. Conclusão: Arsênio, chumbo, mercúrio, manganês, cádmio e estanho são alguns metais envolvidos nos distúrbios neurotoxicológicos. Contudo, fica evidente nesta revisão que são necessários novos estudos a fim de determinar a real associação destes e outros metais nos distúrbios crônicos do sistema nervoso central e periférico.

Introduction: Toxicology is a science that involves innumerable systems and requires a multiprofessional and interdisciplinary team. The clinical indistinctiveness of occupational and non-occupational disorders makes their diagnosis difficult. In this context, occupational and environmental toxicology studies the disorders of the central nervous system (CNS) and the peripheral nervous system (PNS) resulting from intoxication by a wide variety of agents. Method: The method consists of an updated review of the literature based on research in the MEDLINE and LILACS databases, as well as books and documents published online. Results and Discussion: Neuromuscular disorders, movement disorders, motor neuron disease, cognitive-behavioral and neurophysiological alterations have been attributed to innumerable toxic agents in recent years. This article proposes to review the main neurological disorders associated with chronic exposure to metals. To facilitate the initial approach to outpatient treatment of neurotoxicological disorders, tables were devised to describe the main toxic agents, the sources of exposure involved and their main neurological manifestations. Conclusions: Arsenic, lead, mercury, manganese, cadmium and tin are some of the metals involved in neurotoxicological disorders. However, this review reveals the need for new studies to determine the real association of these and other metals in chronic disorders of the central and peripheral nervous systems.

Níveis elevados de manganês e déficit cognitivo em crianças residentes nas proximidades de uma metalúrgica ferro-manganês na região metropolitana de Salvador, Bahia / Elevated levels of manganese and cognitive impairment in children living near a metallurgical iron-manganese in the Metropolitan Region of Salvador, Bahia

As crianças, sobretudo aquelas socialmente vulneráveis, são mais susceptíveis aos efeitos tóxicos da exposição ambiental aos agentes químicos. No processo de desenvolvimento, o sistema nervoso imaturo apresenta grande oportunidade de ação de contaminantes ambientais como o mercúrio (Hg), chumbo (Pb) e o manganês (Mn). Os objetivos desta investigação foram quantificar o grau de exposição ao Mn em crianças residentes nas proximidades de uma planta metalúrgica de ligas ferro-manganês e avaliar a associação entre os níveis deste metal no sangue e no cabelo e efeitos na função cognitiva. Para tal fim, foi realizada uma revisão da literatura científica sobre exposição de crianças ao Mn e efeitos neuropsicológicos, a qual originou o primeiro artigo. A avaliação da exposição ao Mn foi realizada na Vila Cotegipe, no município de Simões Filho, Bahia. Na primeira etapa do trabalho foram obtidas das crianças de 1 a 10 anos amostras de cabelo para determinação do Mn, sangue para hemograma e amostras para parasitológico de fezes. Foram também coletadas amostras ambientais como: água bruta e tratada, material particulado na fração respirável (PM2.5) e poeira domiciliar. Para fins de comparação, crianças de uma comunidade distante 7,5 km da metalúrgica, e a favor dos ventos, foram incluídas como grupo controle Na segunda etapa da avaliação, foram incluídas somente as crianças de 6 a 11 anos e 11 meses matriculadas na escola municipal local. Novas amostras de cabelo e sangue foram coletadas para análise de Mn, chumbo (Pb) e ferro sérico, sendo solicitada a mãe ou responsável a doação da amostra de cabelo. Nessa etapa foi realizada a avaliação cognitiva, através dos instrumentos WISC-III (Wechesler Intelligence Scale for Children), matriz progressiva de Raven para medir a cognição materna e inventário HOME adaptado para estimar o ambiente familiar...

Children, especially those socially vulnerable, are more susceptible to toxic effects resulting from environmental exposure to chemical agents. The developing nervous system has great opportunities to the action of environmental contaminants like mercury (Hg), lead (Pb) and manganese (Mn). The objectives of this research were to evaluate the Mn exposure levels in children living in the vicinity of a ferro-manganese alloy plant and investigate the association between Mn levels in blood and hair with the effects on the cognitive function. Initially, we carried out an intensive literature review on the association between children's exposure to Mn and neuropsychological effects, which led to the first article. The field work started with the populational pool and registration of all families within the limits of the Cotegipe Village, Simões Filho town, Bahia, Brazil. After obtaining the informed consent, we collected socio-demographic data among the volunteers. To assess Mn exposure level, we performed the first sampling campaign with children aged 1 to 10 years: hair samples for Mn determination, blood sample for haemogram and stool for intestinal parasites analyses. At this phase we collected environmental samples: water pre a post treatment, particulate matter from respirable fraction (PM2.5) and house dust. In the second exposure assessment campaign we included only children aged 6 to 11 years and 11 months, enrolled in the local public school, who provided hair and blood samples for Mn, lead and serum iron determination. Mothers or caregivers were asked to provide hair sample. This happened concomitantly with the cognitive evaluation, which was assessed using WISC-III (Wechesler Intelligence Scale for Children), Raven's Progressive Matrices for measuring maternal cognition and the adapted HOME to estimate the family environment stimulation...

Acute toxicity and induced weight changes in laboratory tests with Mn and Cu against Tilapia guineensis (Dumeril) and Tympanotonus fuscatus (Linne).

The acute toxicity of Mn and Cu against Tilapia guineensis and Tympanotonus fuscatus and the sub-lethal effects of the metals on weight changes were investigated in laboratory experiments employing standard bioassay techniques. Based on 96 hr LC50 values, copper was more toxic than manganese to either test animal by several orders of magnitude. Against either test metal, T. guineensis was remarkably more susceptible than T. fuscatus. At sub-lethal concentrations, particularly the two highest concentrations tested (0.016 and 0.03 mg Cu L(-1), 23.0 and 46.0 mg Mn I(-1)), both metals adversely affected the test species by bringing about reduced weight gains or weight loss in exposed animals compared to untreated controls at the end of the test periods. The implications of these findings for ecosystem viability and management are discussed.

Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination

This review attempts to summarize and clarify our basic knowledge as to the various factors that potentially influence the risks imposed from chronic exposure to high atmospheric levels of manganese (Mn). The studies describe the interrelationship of the different systems in the body that regulate Mn homeostasis by characterizing specific, biological components involved in its systemic and cellular uptake and its elimination from the body. A syndrome known as manganism occurs when individuals are exposed chronically to high levels of Mn, consisting of reduced response speed, intellectual deficits, mood changes, and compulsive behaviors in the initial stages of the disorder to more prominent and irreversible extrapyramidal dysfunction resembling Parkinson's disease upon protracted exposure. Mn intoxication is most often associated with occupations in which abnormally high atmospheric concentrations prevail, such as in welding and mining. There are three potentially important routes by which Mn in inspired air can gain access the body to: 1) direct uptake into the CNS via uptake into the olfactory or trigeminal presynaptic nerve endings located in the nasal mucosa and the subsequent retrograde axonal transport directly into the CNS; 2) transport across the pulmonary epithelial lining and its subsequent deposition into lymph or blood; and/or 3) mucocilliary elevator clearance from the lung and the subsequent ingestion of the metal in the gastrointestinal tract. Each of these processes and their overall contribution to the uptake of Mn in the body is discussed in this review as well as a description of the various mechanisms that have been proposed for the transport of Mn across the blood-brain barrier which include both a transferrin-dependent and a transferrin-independent process that may involve store-operated Ca channels.

Intoxicación crónica por exposición laboral a manganeso. Informe de cuatro casos / Chronic toxixity because of occupational exposure to manganese: report of four cases

México ocupa en Latinoamérica el segundo lugar en producción de manganeso, después de Brasil. La exposición laboral de alto riesgo a manganeso se presenta en trabajadores de minas e industrias siderúrgicas. La intoxicación crónica por manganeso se manifiesta por un cuadro clínico similar al de la enfermedad de parkinson. Ante la paradoja en nuesto medio de una detección prácticamente nula de este problema de salud, se describen cuatro casos clínicos identificados en Hidalgo, las variables relacionadas con la exposición laboral al metal y las características clínicas, con el propósito de prevenir a partir de la identificación oportuna del riesgo

Monitoreo biológico en trabajadores expuestos al manganeso / Biological monitoring among workers exposed to manganese

El manganeso es un elemento abundante en el ambiente. Su presentación como dióxido de Mn es la más importante en el comercio y responsable de intoxicaciones crónicas. Su uso más frecuente es en la industria sidermetalúrgica y como funguicida. En el presente trabajo se analiza su metabolismo, el cuadro clínico de la intoxicación aguda y crónica, el diagnóstico diferencial y el tratamiento. Luego de consideraciones sobre el monitoreo ambiental y el monitoreo biológico, se describe un estudio realizado sobre una población de 200 trabajadores de una industria siderometalúrgica de ferroaleaciones, investigados clínicamente y a través del monitoreo biológico con dosaje de manganeso sanguíneo. Se completa el trabajo con consideraciones sobre la determinación de la aptitud laboral en los trabajadores expuestos al manganeso en su ambiente de trabajo

Manganese poisoning reduces strychnine-insensitive glycine binding sites in the globus pallidus of the mouse brain / Reducción de los receptores glicinérgicos insensibles a estricnina en el globo pálido del cerebro de ratones intoxicados con manganeso

Manganese (Mn) poisoning is characterized by central nerous system manifestations, including psychiatric disturbances and estrapyramidal disorders. This metal is thought to produce neuronal degeneration due to cytotoxic products originated by oxidative stress and through an indirect excitotoxic process. In previous studies, we have found a reduction in the density of N-methyl-D-aspartate (NMDA) recognition sites in some brain areas of Mn-treated mice. Due to the close relationship between NMDA receptor complex, the [3H]-glycine ([3H]/Gly) binding was manganese choride for 8 weeks. Among all analyzed areas, only the globus pallidus showed a significant reduction in [3H]-Gly binding (27-28). The Gly binding decrease, focalized in the globus pallidus, could reflect a degeneration of structures containing strychnine-insensitive Gly receptors, since this area is the most frequently reported damaged brain region in Mn intoxication. Howerer, it might also be due to a Gly receptor down-regulation to control NMDA complex activation during Mn poisoning.

Intoxicación crónica con manganeso: cuantificación autorradiográfica de los receptores colinérgicos muscarínicos en el cerebro de ratón / Chronic manganese poisoning: autoradiograohic cuantitation of muscarinic cholinergic receptors in mouse brain

El tratamiento crónico con cloruro de manganeso (5 mg Mn/kg/día), durante 9 semanas, no afectó la unión del radioligando [3H]-quinuclidinil benzilato a los receptores colinérgicos muscarínicos en el cerebro de ratón. Mediante técnica autorradiográfica se determinó la localización anatómica precisa de los receptores y se procedió a la cuantificació de los mismos en los cortes coronales del bulbo olfatorio y del cerebro medio. A la luz de los resultados obtenidos podemos concluir que, en nuestras condiciones experimentales, no se producen alteraciones en la densidad de los receptores colinérgicos muscarínicos en el cerebro de ratones intoxicados con manganeso

Intoxicación crónica con manganeso: avances recientes; revisión / Chronic manganese poisoning: recent advances; review

La intoxicación crónica con manganeso es una enfermedad que ha sido considerada como un modelo de bradicinesia extrapiramidal acompañada de un síndrome distónico de naturaleza estriatal. Desde el punto de vista anatomopatológico, la lesión más característica es la destrucción celular del caudado, putamen y globo pálido. Las neuronas dopaminérgicas y noradrenérgicas son las más sensibles al efecto tóxico del manganeso, aunque también se han reportado alteraciones en las neuronas serotoninérgicas y, en menor intensidad, en las GABA-érgicas. Las neuronas colinérgicas, por el contrario, son muy resistentes a la intoxicación crónica con el metal. Los efectos observables en los animales de experimención son muy variables y dependen de la especie animal, dosis y vía de administración del metal y duración del tratamiento. Al parecer, la degeneración de las neuronas catecolaminérgicas se debe al incremento en la oxidación de las catecolaminas, lo cual produciría la generación de semiquinonas, ortoquinomas y los radicales superóxido, peróxido de hidrógeno e hidroxilo. Esta "catálisis regenerativa" originaría la destrucción de estas neuronas, mediante el aumento de la peroxidación lipídica, alteraciones del ADN y la inhibición de las enzimas sulfidrilas