RESUMO
A mutation of the DYT1 gene, which codes for torsinA, has been identified as the cause of one form of autosomal dominantly inherited dystonia. TorsinA immunohistochemistry was used to examine a case of DYT1, and several cases of non-DYT1, dystonia. No evidence was found for alterations of immunoreactivity at the light microscopic level, specifically neither cytoplasmic aggregations nor colocalization of torsinA immunoreactivity with a marker for endoplasmic reticulum. These findings contrast with results of recent cell culture studies of torsinA.
Assuntos
Encéfalo/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Distúrbios Distônicos/genética , Distúrbios Distônicos/metabolismo , Chaperonas Moleculares , Mutação , Adulto , Encéfalo/patologia , Citoplasma/metabolismo , Distúrbios Distônicos/patologia , Retículo Endoplasmático/metabolismo , Humanos , Imuno-Histoquímica , MasculinoRESUMO
Patients with parkinsonism-dementia complex (PDC) of Guam showed moderate loss of choline acetyl transferase activity in the midfrontal and inferior parietal cortex, and severe loss in the superior temporal cortex. This deficit was similar to that seen in Alzheimer's disease and less severe than Lewy body disease. Thus, cholinergic deficits in the neocortex might contribute to some of the cognitive alterations in PDC of Guam.
Assuntos
Colina O-Acetiltransferase/metabolismo , Neocórtex/enzimologia , Doença de Parkinson/metabolismo , Acetilcolina/metabolismo , Idoso , Doença de Alzheimer/metabolismo , Gânglios da Base/enzimologia , Feminino , Lobo Frontal/enzimologia , Guam , Humanos , Doença por Corpos de Lewy/metabolismo , Masculino , Lobo Parietal/enzimologia , Terminações Pré-Sinápticas/metabolismo , Lobo Temporal/enzimologiaRESUMO
The unbiased sampling techniques of stereology have been developed to avoid the inaccuracies of using 'representative' sections for morphometric studies. In order to carry out a stereologically valid study, the region of interest must be fully available for sampling and its boundaries or its constituents must also be distinctly identifiable. However, in the setting of a brain bank in which only one half of the brain specimen is fixed for morphology, a logistic problem arises in satisfying the needs of the diagnostic neuropathologist with that of the stereologically oriented morphologist. We present a dissection approach in which the region for analysis must be used for unbiased sampling and also be available for paraffin-embedded neuropathologic work-up. Following fixation, a block consisting of the entire region of interest is removed intact and using a multibladed knife the block is subsectioned in the coronal plane at regular intervals. Alternate blocks are chosen for either paraffin embedding and destined to neuropathologic evaluation or are processed for stereology. The stereology blocks can be either cryoprotected or placed in phosphate buffer and are serially sectioned on a cryostat or a Vibratome. Preliminary analyses using this approach have provided reliable estimates of the total number of different neuronal populations and disease-related lesions in a variety of human and non-human banked specimens. In addition, this approach has definite advantages in that it provides rigorous quantitative estimates of neuropathologic changes that can be correlated to clinical data and does not compromise the routine neuropathological diagnostic procedure of the materials.
Assuntos
Envelhecimento/patologia , Encéfalo/anatomia & histologia , Doenças do Sistema Nervoso/patologia , Bancos de Tecidos , Animais , Corantes , Córtex Entorrinal/anatomia & histologia , Córtex Entorrinal/patologia , Hominidae/anatomia & histologia , Humanos , Microtomia , Manejo de Espécimes , Substância Negra/anatomia & histologia , Substância Negra/patologia , Fixação de TecidosRESUMO
Parkinson's disease (PD) is a neurodegnerative disorder that is pathologically characterized by the presence of Lewy bodies in the brain. We show that Lewy bodies in PD are strongly immunoreactive for torsinA, the protein product of the DYT1 gene, which is associated with primary generalized dystonia. In the substantia nigra, torsinA immunoreactivity is localized to the periphery of Lewy bodies, whereas, in cortical Lewy bodies it is uniformly distributed. The significance of this finding is unknown, but may implicate torsinA in neuronal dysfunction that occurs in PD as well as in primary dystonia.
Assuntos
Proteínas de Transporte/metabolismo , Córtex Cerebral/metabolismo , Corpos de Lewy/metabolismo , Chaperonas Moleculares , Neurônios/metabolismo , Doença de Parkinson/metabolismo , Substância Negra/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Humanos , Corpos de Lewy/patologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Substância Negra/patologia , Substância Negra/fisiopatologia , SinucleínasRESUMO
Oxidative stress has been proposed as a pathogenetic mechanism in Parkinson's disease (PD). One mechanism of oxidative cellular injury is the nitration of protein tyrosine residues, mediated by peroxynitrite, a reaction product of nitric oxide and superoxide radicals. We demonstrate here the presence of nitrotyrosine immunoreactivity in Lewy bodies within melanized neurons and in amorphous deposits associated with intact and degenerating neurons. The core of the Lewy body was frequently intensely immunolabeled, while the rim was lightly labeled or unlabeled. This likely reflects the fact that tyrosine residues of neurofilament proteins are primarily localized to Lewy body cores, and suggests that nitrotyrosine is present in neurofilament protein itself. Although these observations are as yet unable to provide a definitive link between oxidative stress and neuronal dysfunction, they demonstrate that oxidative stress has occurred within the vulnerable neurons of PD, leaving a permanent marker of oxidative modification of neuronal proteins within the target cells of neurodegeneration. In addition, these observations provide a potential link between excitotoxicity and oxidative stress within the vulnerable neurons of PD and represent a pathogenetic mechanism in common with the 2 other major age-related neurodegenerative diseases, Alzheimer disease and amyotrophic lateral sclerosis.
Assuntos
Neurônios/metabolismo , Doença de Parkinson/metabolismo , Substância Negra/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Imuno-Histoquímica , Corpos de Lewy/metabolismo , Pessoa de Meia-Idade , Neurônios/patologia , Estresse Oxidativo , Doença de Parkinson/patologia , Substância Negra/patologiaRESUMO
We report a laser microprobe mass analysis of aluminum and iron content in the hippocampus and in the inferior temporal cortex in 2 cases of dementia pugilistica (DP), 4 cases of Alzheimer's disease (AD), and 3 controls. There was a predominant accumulation of Al and Fe within neurofibrillary tangles (NFT) in both DP and AD cases. High levels of Al and Fe were also detected in the nuclei of NFT-free and NFT-containing neurons, as well as in neuropil probe sites in these cases. In both regions, NFT contained substantially higher levels of Al and Fe in DP compared to AD cases. These findings suggest the existence of an association between the deposition of Al and Fe and NFT formation, and support the possibility of a global dysregulation of Al and Fe transport in DP and AD.
Assuntos
Alumínio/análise , Doença de Alzheimer/patologia , Boxe/lesões , Química Encefálica , Encéfalo/patologia , Demência/patologia , Ferro/análise , Lasers , Doenças Profissionais/patologia , Idoso , Doença de Alzheimer/fisiopatologia , Estudos de Casos e Controles , Demência/etiologia , Demência/fisiopatologia , Hipocampo/química , Hipocampo/patologia , Humanos , Pessoa de Meia-Idade , Fibras Nervosas/química , Fibras Nervosas/patologia , Emaranhados Neurofibrilares/química , Emaranhados Neurofibrilares/patologia , Neurônios/química , Neurônios/patologia , Doenças Profissionais/fisiopatologia , Lobo Temporal/química , Lobo Temporal/patologiaRESUMO
We report a detailed analysis of the content of aluminum, iron, zinc, copper, calcium, and magnesium in the non-vascular and pericapillary mineralizations and the normal capillaries of the globus pallidus and dentate nucleus of the cerebellum in two patients with clinically and neuropathologically confirmed Fahr's disease. The study employed laser microprobe mass analysis, a technique that enables highly sensitive detection of the levels of trace elements. In the globus pallidus, there was a significant increase in aluminum-, iron-, zinc-, and calcium-related peak intensity in the pericapillary and non-vascular mineralizations compared to the normal capillaries. The pericapillary and non-vascular mineralizations had comparable concentrations of these elements. No difference was found in copper levels between the different probe sites. Magnesium was almost absent in pericapillary mineralizations and normal capillaries, while it accumulated within non-vascular mineralizations. In the cerebellar dentate nucleus, non-vascular mineralizations displayed higher concentrations of all of these elements than normal capillaries, while pericapillary mineralizations had a higher aluminum and lower iron, copper, and calcium content than did non-vascular mineralizations. Zinc and magnesium were selectively deposited within the non-vascular mineralizations in this nucleus. Furthermore, the element composition of non-vascular mineralizations differed between the globus pallidus and dentate nucleus. These findings indicate that the formation of pericapillary and non-vascular mineralizations may be two independent phenomena which coexist in the course of Fahr's disease. The marked qualitative and quantitative differences in trace element content in non-vascular mineralizations between the globus pallidus and cerebellar dentate nucleus suggest that the involvement of trace elements in the pathogenesis of Fahr's disease is probably indirect.
Assuntos
Doenças dos Gânglios da Base/fisiopatologia , Química Encefálica/fisiologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Calcinose/fisiopatologia , Capilares/química , Oligoelementos/análise , Idoso , Idoso de 80 Anos ou mais , Alumínio/análise , Cálcio/análise , Cobre/análise , Feminino , Humanos , Ferro/análise , Lasers , Magnésio/análise , Masculino , Espectrometria de Massas/métodos , Zinco/análiseRESUMO
Oxidative stress has been proposed as a pathogenetic mechanism in Alzheimer's disease. One mechanism of oxidative damage is the nitration of tyrosine residues in proteins, mediated by peroxynitrite breakdown. Peroxynitrite, a reaction product of nitric oxide and superoxide radicals, has been implicated in N-methyl-D-aspartate receptor-mediated excitotoxic damage. Reported evidence of oxidative stress in Alzheimer's disease includes increased iron, alterations in protective enzymes, and markers of oxidative damage to proteins and lipids. In this report, we demonstrate the presence of nitrotyrosine in neurofibrillary tangles of Alzheimer's disease. Nitrotyrosine was not detected in controls lacking neurofibrillary tangles. Immunolabeling was demonstrated to be specific nitrotyrosine in a series of control experiments. These observations link oxidative stress with a key pathological lesion of Alzheimer's disease, the neurofibrillary tangle, and demonstrate a pathogenetic mechanism in common with the other major neurodegenerative diseases of aging, Parkinson's disease and amyotrophic lateral sclerosis. These findings further implicate nitric oxide expression and excitotoxicity in the pathogenesis of cell death in Alzheimer's disease.
Assuntos
Doença de Alzheimer/patologia , Neurônios/patologia , Estresse Oxidativo/fisiologia , Tirosina/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/etiologia , Doença de Alzheimer/fisiopatologia , Anticorpos Monoclonais , Córtex Cerebral/patologia , Pré-Escolar , Hipocampo/patologia , Humanos , Imuno-Histoquímica , Recém-Nascido , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/patologia , Neurônios/fisiologia , Tirosina/análiseRESUMO
We gave three adult rhesus monkeys seven IV injections of manganese chloride at approximately 1-week intervals. We evaluated neurologic status by serial clinical examinations and performed a levodopa test if the animal developed features of basal ganglia dysfunction. After the animals were killed, we performed neuropathologic, neurochemical, and laser microprobe mass analysis (LAMMA) studies. Two of three animals developed a parkinsonian syndrome characterized by bradykinesia, rigidity, and facial grimacing suggestive of dystonia but not tremor. Neither animal responded to levodopa. Autopsy demonstrated gliosis primarily confined to the globus pallidus (GP) and the substantia nigra pars reticularis (SNr). We detected focal mineral deposits throughout the GP and SNr, particularly in a perivascular distribution. LAMMA studies noted that mineral deposits were primarily comprised of iron and aluminum. The severity of pathologic change correlated with the degree of clinical dysfunction. These studies demonstrate that, in contrast to Parkinson's disease (PD) and MPTP-induced parkinsonism, manganese primarily damages the GP and SNr and relatively spares the nigrostriatal dopaminergic system. Further, the results suggest that Mn-induced parkinsonism can be differentiated from PD and MPTP-induced parkinsonism by the clinical syndrome and response to levodopa. The accumulation of iron and aluminum suggests that iron/aluminum-induced oxidant stress may contribute to the damage associated with Mn toxicity.
Assuntos
Gânglios da Base/efeitos dos fármacos , Encéfalo/patologia , Cloretos/toxicidade , Compostos de Manganês , Intoxicação por Manganês , Doença de Parkinson Secundária/induzido quimicamente , Animais , Gânglios da Base/patologia , Encéfalo/efeitos dos fármacos , Carbidopa/farmacologia , Cloretos/intoxicação , Gliose/patologia , Globo Pálido/efeitos dos fármacos , Globo Pálido/patologia , Levodopa/farmacologia , Macaca mulatta , Masculino , Doença de Parkinson Secundária/patologia , Doença de Parkinson Secundária/fisiopatologia , Intoxicação/patologia , Substância Negra/efeitos dos fármacos , Substância Negra/patologiaRESUMO
Laser microprobe mass analysis (LAMMA) is an investigational method which is a powerful tool for the identification and quantitation of various elements present in small volumes of tissue. LAMMA is highly sensitive and capable of rapidly detecting concentrations of 1-3 p.p.m. of most metallic elements, in precisely localized cellular compartments. In order to further assess its value, cultured skin fibroblasts and biopsy tissues from human subjects and experimental animals were probed by LAMMA, and the results were correlated with ultrastructural findings. Biopsy samples were obtained from patients suffering from Gaucher disease, and from patients and animals with pathologic iron or copper metabolism. No significant abnormalities were detected in the cultured fibroblasts from patients with Gaucher disease, in contrast to the iron content of tissue biopsy Gaucher cells, which was markedly increased, apparently as a consequence of erythrophagocytosis. Particularly intense iron-related peaks were found in liver cytosiderosis due to neonatal or genetic haemochromatosis, thalassaemia major and in animal models of iron overload. An additional finding was the presence of aluminium accumulation in siderosomes of different cells. In liver biopsy samples from human Wilson's disease and from rats with an inherited disorder causing copper toxicosis, copper-containing compounds were identified and localized, and their relative concentration was estimated by LAMMA. The present study showed that LAMMA is a valuable technique for the localization and estimation of relative abundance of trace elements in various tissues containing excessive amounts of metals.
Assuntos
Doença de Gaucher , Espectrometria de Massas/métodos , Oligoelementos/análise , Animais , Biópsia , Cobre/análise , Ferritinas/análise , Fibroblastos/química , Doença de Gaucher/patologia , Hemocromatose/genética , Degeneração Hepatolenticular/patologia , Humanos , Ferro/análise , Lasers , Fígado/química , Camundongos , Microscopia Eletrônica , Papio , Ratos , Talassemia/patologiaRESUMO
Homozygote hypotransferrinaemic mice (hpx/hpx) have cytopathological features similar to those of human congenital atransferrinaemia, genetic haemochromatosis, and neonatal haemochromatosis. These conditions all have in common high levels of cytotoxic non-transferrin-bound serum iron. This study describes the ultrastructural features of iron overload in liver, pancreas, heart, and small intestine of 2- and 12-month-old hypotransferrinaemic mice. Electron microscopic studies of unstained sections showed early parenchymal cell siderosis, with accumulation of numerous ferritin particles and clusters in the cytosol, as well as ferritin and haemosiderin in lysosomes (siderosomes). In the 12-month-old animals, iron was also found in Kupffer cells and macrophages in other tissues. In addition, there were conspicuous iron-containing compounds in the bile canaliculi, and marked iron deposition in the pancreas and heart. Laser microprobe mass analysis (LAMMA) enabled localization and relative quantitation of iron deposition in subcellular compartments providing in situ documentation of iron accumulation in siderosomes and contributed in assessing total cytosolic iron in various cell types. Moreover, it demonstrated the importance and magnitude of the biliary route for iron excretion in these animals.
Assuntos
Hemocromatose/patologia , Hemossiderose/patologia , Transferrina/metabolismo , Animais , Hemocromatose/metabolismo , Hemossiderose/metabolismo , Ferro/análise , Lasers , Espectrometria de Massas , Camundongos , Camundongos Mutantes , Microscopia Eletrônica , Distribuição TecidualRESUMO
Projections of the entorhinal cortex to the hippocampus are well known from the classical studies of Cajal (Ramon y Cajal, 1904) and Lorente de Nó (1933). Projections from the entorhinal cortex to neocortical areas are less well understood. Such connectivity is likely to underlie the consolidation of long-term declarative memory in neocortical sites. In the present study, a projection arising in layer V of the entorhinal cortex and terminating in a polymodal association area of the superior temporal gyrus has been identified with the use of retrograde tracing. The dendritic arbors of neurons giving rise to this projection were further investigated by cell filling and confocal microscopy with computer reconstruction. This analysis demonstrated that the dendritic arbor of identified projection neurons was largely confined to layer V, with the exception of a solitary, simple apical dendrite occasionally ascending to superficial laminae but often confined to the lamina dissecans (layer IV). Finally, immunoreactivity for glutamate-receptor subunit proteins GluR 5/6/7 of the dendritic arbor of identified entorhinal projection neurons was examined. The solitary apical dendrite of identified entorhinal projection neurons was prominently immunolabeled for GluR 5/6/7, as was the dendritic arbor of basilar dendrites of these neurons. The restriction of the large bulk of the dendritic arbor of identified entorhinal projection neurons to layer V implies that these neurons are likely to be heavily influenced by hippocampal output arriving in the deep layers of the entorhinal cortex. Immunoreactivity for GluR 5/6/7 throughout the dendritic arbor of such neurons indicates that this class of glutamate receptor is in a position to play a prominent role in mediating excitatory neurotransmission within hippocampal-entorhinal circuits.
Assuntos
Córtex Cerebral/citologia , Córtex Entorrinal/citologia , Macaca fascicularis/anatomia & histologia , Neurônios/ultraestrutura , Receptores de Ácido Caínico/análise , Amidinas , Animais , Córtex Cerebral/metabolismo , Dendritos/ultraestrutura , Córtex Entorrinal/química , Corantes Fluorescentes , Imunoglobulina M , Isoquinolinas , Macaca fascicularis/metabolismo , Masculino , Vias Neurais/química , Vias Neurais/ultraestrutura , Neurônios/química , Receptores de Glutamato/análiseRESUMO
This case study reports our clinical and laboratory investigation of the accidental death of a pregnant rural woman related to phosphine exposure from stored grain fumigated with aluminum phosphide (AIP3) pellets. Environmental data (housing proximity to fumigated grain and meteorologic conditions at the time) coupled with clinical data (tachycardia and the rapid development of pulmonary edema with no antecedent clinical abnormalities) suggested possible toxicant effects. Gross and microscopic autopsy findings demonstrated pulmonary edema. Because phosphine generated from the phosphide is highly reactive and unstable, our laboratory strategy for this investigation focused on the quantitative analysis of aluminum (AI) in blood, gastric contents, and in lung tissue to test the possibility of fumigant intoxication. We recovered 713 ng/ml Al from blood (normal laboratory range 2 to 42 ng/ml). Laser mass spectral analysis of lung tissue demonstrated high concentrations of Al in alveolar macrophages (> 200 ppm) with little or no Al in adjacent lung tissue. Control lung tissue from an urban autopsy case matched by age, sex, and smoking habits showed no demonstrable Al. We conclude that Al may be a useful marker for AIP3 exposure.
Assuntos
Compostos de Alumínio/intoxicação , Alumínio/análise , Exposição Ambiental , Praguicidas/intoxicação , Fosfinas/intoxicação , Complicações na Gravidez/induzido quimicamente , Adulto , Alumínio/sangue , Evolução Fatal , Feminino , Fumigação , Humanos , Pulmão/química , Macrófagos Alveolares/química , Gravidez , Saúde da População RuralRESUMO
A monoclonal antibody specific for GluR5-7 (mAb-4F5) has been used to characterize the distribution of kainate class glutamate receptor subunits in monkey hippocampus. Immunolabeled neurons were present in all subfields of the hippocampus as well as the dentate gyrus and subiculum. Quantitative immunofluorescence analysis by confocal microscopy demonstrated differential levels of immunoreactivity such that the highest intensities were in neurons within CA1 and subiculum as compared with those within CA3 or dentate gyrus. The regional differences in levels of subunit immunoreactivity correlate with the relative vulnerability of hippocampal neurons in several neurodegenerative disorders.
Assuntos
Hipocampo/metabolismo , Receptores de Glutamato/metabolismo , Receptores de Ácido Caínico/metabolismo , Animais , Anticorpos Monoclonais , Gráficos por Computador , Imunofluorescência , Hipocampo/ultraestrutura , Macaca fascicularis , Microscopia Imunoeletrônica , Neurônios/metabolismoRESUMO
The Laser Microprobe Mass Analyzer (LAMMA) is a sensitive instrument for identifying and localizing trace elements in tissue samples. Using LAMMA, we have examined melanin-containing neurons of the substantia nigra in patients with Parkinson's disease (PD) and controls. We found that iron significantly accumulates within neuromelanin granules of patients with PD compared to controls. Increased aluminum was found in the neuromelanin granules of 2 of 3 PD cases but in no controls. The accumulation of iron and aluminum, which are known to promote oxidant stress, may account for the selective degeneration of neuromelanin-containing neurons in PD.
Assuntos
Alumínio/metabolismo , Ferro/metabolismo , Melaninas/análise , Neurônios/patologia , Doença de Parkinson/patologia , Substância Negra/patologia , Oligoelementos/metabolismo , Alumínio/análise , Humanos , Ferro/análise , Lasers , Espectrometria de Massas/métodos , Neurônios/metabolismo , Doença de Parkinson/metabolismo , Valores de Referência , Substância Negra/metabolismo , Oligoelementos/análiseRESUMO
We report the results of an examination of the elemental content of neurofibrillary tangle-bearing and neurofibrillary tangle-free neurons identified within the hippocampus of 10 subjects with Alzheimer's disease and 4 neuropathologically intact age-matched control subjects. The study employed laser microprobe mass analysis (LAMMA), a technique that provides extremely sensitive multielement detection in plastic-embedded, semithin-sectioned tissues. Evidence for the selective accumulation of aluminum within the neurofibrillary tangle-bearing neurons was obtained in all 10 subjects with Alzheimer's disease. The site of aluminum deposition within these cells was the neurofibrillary tangle itself, and not the "nuclear region," as we previously reported. Iron accumulation was also detected within neurofibrillary tangles. Evaluation for the accumulation of other elements within the tangle-bearing neurons failed to reveal any other metallic element as being consistently present. In addition, probe sites directed to neurons identified in snap-frozen cryostat sections from 2 subjects with Alzheimer's disease revealed similar spectra with prominent aluminum-related peaks, confirming that our findings are not related to exogenous contamination through fixation, embedding, or other procedures prior to analysis. This study further confirms the association of aluminum and neurofibrillary tangle formation in Alzheimer's disease.
Assuntos
Alumínio/metabolismo , Doença de Alzheimer/metabolismo , Ferro/metabolismo , Espectrometria de Massas/métodos , Emaranhados Neurofibrilares/metabolismo , Núcleo Celular/química , Citoplasma/química , Humanos , LasersRESUMO
Iron is essential for a number of normal brain functions and accumulates in high concentrations in specific regions of the brain. In pathological states, it may further accumulate in these and other areas that are typically low in iron content. The contribution of excess iron to potential central nervous system damage through its ability to donate an electron and to promote oxygen free radical formation has made the nature, location, extent, and process of iron deposition in the brain important areas of investigation. Nevertheless, there is relatively little information currently available on the cellular and subcellular distribution of iron in the central nervous system in either normal or diseased states. We describe and compare a number of the currently available techniques by which iron can be detected within the cellular components of the brain. Histochemical approaches, primarily in the form of the Perls' stain, yields information only on iron in its ferric state and is a relatively insensitive technique. Electron microscopy with x-ray spectrometry can provide positive identification of iron but has limitations regarding morphological verification of the specific cells being probed and also has a relatively high lowest detection limit. Secondary ion mass spectrometry and proton-induced x-ray spectrometry are both expensive, highly complex techniques with greater detection sensitivity, but they have problems identifying the cellular components being analyzed. Finally, laser microprobe mass analysis combines histological localization and identification of probe sites in plastic-embedded histological sections with detection limits in the single part per million range.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Química Encefálica , Ferro/análise , Animais , Encéfalo/citologia , Microanálise por Sonda Eletrônica , Histocitoquímica , Humanos , Lasers , Espectrometria de Massas , Espectrometria por Raios X , Análise Espectral/métodosRESUMO
Despite the contradictory results of studies attempting to compare the bulk brain tissue aluminium content of specimens from Alzheimer's disease patients and controls, microprobe studies from our laboratory have consistently documented evidence of selective accumulation of the element within the neurofibrillary tangle-bearing cells associated with this condition. Laser microprobe mass analysis (a highly sensitive and precise technique for trace elemental microprobe analysis) has now demonstrated that the most prominent aluminium accumulations occur within the neurofibrillary tangle itself. Similar findings have been obtained from microprobe studies of the neurofibrillary tangles which are a characteristic feature of amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. Although the intraneuronal localization of aluminium in the Guam-derived specimens is similar to that of Alzheimer's disease, the concentration of aluminium is considerably higher than is encountered in Alzheimer's disease specimens. We conclude that aluminium is an integral component of the neurofibrillary tangle and raise the possibility that the cross-linking properties of this highly reactive metal may stabilize the constituent cytoskeletal proteins which make up this pathological structure.