RESUMO
A current hypothesis about methylmercury (MeHg) neurotoxicity proposes that neuronal damage is due to excitotoxicity following glutamate uptake alterations in the astrocyte. By sampling from a microdialysis probe implanted in the frontal cortex of adult Wistar rats, we measured the effects of acute exposure to either 10 or 100 microM MeHg through the microdialysis probe, on glutamate extracellular levels in 15 awake animals. After baseline measurements, the perfusion of MeHg during 90 min induced immediate and significant elevations in extracellular glutamate at 10 microM (9.8-fold, P<.001) and at 100 microM (2.4-fold, P=.001). This in vivo demonstration of increments of extracellular glutamate supports the hypothesis that dysfunction of glutamate neurotransmission plays a key role in MeHg-induced neural damage.
Assuntos
Astrócitos/efeitos dos fármacos , Espaço Extracelular/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Intoxicação do Sistema Nervoso por Mercúrio/metabolismo , Compostos de Metilmercúrio/toxicidade , Regulação para Cima/efeitos dos fármacos , Animais , Astrócitos/metabolismo , Relação Dose-Resposta a Droga , Espaço Extracelular/metabolismo , Feminino , Lobo Frontal/metabolismo , Lobo Frontal/fisiopatologia , Intoxicação do Sistema Nervoso por Mercúrio/patologia , Intoxicação do Sistema Nervoso por Mercúrio/fisiopatologia , Microdiálise , Degeneração Neural/induzido quimicamente , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Regulação para Cima/fisiologiaRESUMO
Endosulfan (ES) and methyl parathion (MP) are widely used in Latin America, and simultaneous exposure to both products is documented. This exposure may have effects on the nervous system because their targets include the GABAergic and cholinergic systems, which are main modulators of neuronal excitability in the cortex and hippocampus. We tested whether low-level, repeated exposure of adult rats to commercial formulations containing ES and MP disrupts spatial learning in the water maze. Five groups of eight animals received subcutaneously appropriate dilutions of the commercial formulations to yield the following treatments during 10 days: saline, 25 mg/kg ES, 2 mg/kg MP (MP(2)), 25 mg/kg ES plus 1 mg/kg MP (ES+MP(1)) and 25 mg/kg ES plus 2 mg/kg MP (ES+MP(2)). In addition, markers of neurological function, renal and hepatic damage were explored as potential consequences of exposure. In the absence of overt toxicity, the groups exposed to the ES plus MP showed significantly longer escape latencies, higher number of failures to reach the platform and more time in the periphery of the tank than the control and single-exposed groups. This finding shows that commercial formulations of ES and MP have marginal effects when administered individually but can produce behavioral alterations when given in combination.
Assuntos
Endossulfano/toxicidade , Exposição Ambiental/efeitos adversos , Inseticidas/toxicidade , Deficiências da Aprendizagem/induzido quimicamente , Metil Paration/toxicidade , Resíduos de Praguicidas/toxicidade , Acetilcolinesterase/sangue , Acetilcolinesterase/efeitos dos fármacos , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Interações Medicamentosas/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Deficiências da Aprendizagem/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Rigidez Muscular/induzido quimicamente , Rigidez Muscular/fisiopatologia , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologiaRESUMO
We studied the effects of chronic arsenic exposure on brain monoamines and plasma levels of adrenocorticotropic hormone (ACTH) of mice. After weaning, mice received arsenic (0, 20, 40, 60 or 100 ppm) in drinking water over a period of 9 weeks. Monoamine content was quantified in different brain regions, arsenic was quantified in brain tissue and ACTH levels in plasma. Brain arsenic concentrations up to 200 ng/g showed a significant correlation with exposure levels and produced slight modifications in regional monoamine levels. ACTH plasma levels were significantly associated with norepinephrine (NE) concentrations in the medulla and pons, but not with hypothalamic NE levels. ACTH levels were significantly higher in the group exposed to 20 ppm. Dopamine showed significant dose-related decreases in the hypothalamus. These results show that chronic sodium arsenite exposure produces changes in central monoamines, which are not associated on a dose-dependent basis with major alterations in plasma ACTH.
Assuntos
Hormônio Adrenocorticotrópico/efeitos dos fármacos , Arsenitos/toxicidade , Monoaminas Biogênicas/metabolismo , Química Encefálica/efeitos dos fármacos , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Ácido Hidroxi-Indolacético/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Bulbo/efeitos dos fármacos , Bulbo/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Norepinefrina/metabolismo , Ponte/efeitos dos fármacos , Ponte/metabolismo , Serotonina/metabolismoRESUMO
Several single components of mining waste (arsenic, manganese, lead, cadmium) to which humans are exposed at the mining area of Villa de la Paz, Mexico, are known to provoke alterations of striatal dopaminergic parameters. In this study we used an animal model to examine neurochemical changes resulting from exposure to a metal mixture. We used microdialysis to compare in vivo dopamine release from adult rats subchronically exposed to a mining waste by oral route with those from a control group and from a sodium arsenite group (25 mg/kg/day). We found that arsenic and manganese do accumulate in rat brain after 2 weeks of oral exposure. The mining waste group showed significantly decreased basal levels of dihydroxyphenylacetic acid (DOPAC; 66.7 +/- 7.53 pg/ microl) when compared to a control group (113.7 +/- 14.3 pg/ microl). Although basal dopamine release rates were comparable among groups, when the system was challenged with a long-standing depolarization through high-potassium perfusion, animals exposed to mining waste were not able to sustain an increased dopamine release in response to depolarization (mining waste group 5.5 +/- 0.5 pg/ microl versus control group 21.7 +/- 5.8 pg/ microl). Also, DOPAC and homovanillic acid levels were significantly lower in exposed animals than in controls during stimulation with high potassium. The arsenite group showed a similar tendency to that from the mining waste group. In vivo microdialysis provides relevant data about the effects of a chemical mixture. Our results indicate that this mining waste may represent a health risk for the exposed population.
Assuntos
Dopamina/metabolismo , Resíduos Perigosos/efeitos adversos , Metais Pesados/toxicidade , Neostriado/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Administração Oral , Animais , Masculino , México , Microdiálise , Mineração , Neostriado/metabolismo , Ratos , Ratos WistarRESUMO
Dot-ELISA and standard-ELISA were used to detect T. solium cysticercus antigens in cerebrospinal fluid for the diagnosis of neurocysticercosis. The results indicate that both assays are sensitive, specific and economically adequate for the diagnosis of this disease. Using SDS-PAGE, electroblotting and dot-ELISA we have found that the antigen is a protein with a molecular weight of 66,000 daltons.
Assuntos
Antígenos de Helmintos/líquido cefalorraquidiano , Cisticercose/diagnóstico , Taenia/imunologia , Adulto , Animais , Criança , Ensaio de Imunoadsorção Enzimática , HumanosRESUMO
La frecuencia elevada de cisticersosis en paises en desarrollo y sus efectos patologicos y economicos senalan la necesidad de contar con una prueba satisfactoria para diagnosticar esta enfermedad. En el Hospital Central Ignacio Morones Prieto de San Luis Potosi, SLP, Mexico, se realizo un estudio en el que se comparo la sensibilidad del ensayo inmunosorbente enzima conjugada (ELISA) con la del metodo de hermaglutinacion indirecta (HI), para diagnosticar la cisticercosis. Por medio de ambos metodos se analizaron muestras de liquido cefalorraquideo y de suero de 120 pacientes neurologicos que se dividieron en dos grupos control y un grupo de 17 casos de cisticercosis cerebral confirmada. Las muestras de los grupos control resultaron negativas con ambos procedimientos, pero en el grupo de enfermos de cisticercosis con el metodo de HI se obtuvo 29% de resultados falsos negativos, en tanto que con ELISA no se obtuvo ninguno.Se concluye que el metodo ELISA es mas sensible que el de HI puesto que con el no se lograron resultados falsos negativos ni positivos sin embargo, en vista del pequeno numero de casos investigados no es posible llegar a una conclusion definitiva