RESUMO
Radiation damage upon soft X-ray exposure is an important issue to be considered in soft X-ray microscopy. The work presented here is part of a more extended study on the topic and focuses on the effects of soft X-rays on paraffin, a common embedding medium for soft-tissues, and on ultralene and Si3N4 windows as sample supports. Our studies suggest that the sample environment indeed plays an important role in the radiation damage process and therefore should be carefully taken into account for the analysis and interpretation of new data. The radiation damage effects were followed over time using a combination of Fourier transform infrared (FTIR) microspectroscopy and X-ray fluorescence (XRF), and it was demonstrated that, for higher doses, an oxidation of both embedding medium and ultralene substrate takes place after the irradiated sample is exposed to air. This oxidation is reflected in a clear increase of C=O and O-H infrared bands and on the XRF oxygen maps, correlated with a decrease of the aliphatic infrared signal. The results also show that the oxidation process may affect quantitative evaluation of light element concentrations.
Assuntos
Parafina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Fluorescência , Oxirredução , Inclusão em Parafina , Raios XRESUMO
Ganstigmine (CHF2819) is an acetylcholinesterase inhibitor that increases acetylcholine in rat hippocampus and ameliorates scopolamine-induced amnesia. In this article, we examined whether and how ganstigmine might prevent or rescue the neurodegenerative phenotype in AD11 antinerve growth factor (anti-NGF) mice, a transgenic model for Alzheimer's disease. The effects of ganstigmine were compared with those obtained after administration of donepezil. Results demonstrate that intraperitoneal and oral administration of ganstigmine and donepezil can reverse the cholinergic and behavioral deficit in AD11 mice but not the amyloid and phosphotau accumulation, uncovering different mechanisms leading to neurodegeneration in AD11 mice.
Assuntos
Alcaloides/farmacologia , Alcaloides/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Indanos/farmacologia , Indanos/uso terapêutico , Degeneração Neural/tratamento farmacológico , Degeneração Neural/patologia , Fator de Crescimento Neural/antagonistas & inibidores , Fator de Crescimento Neural/efeitos dos fármacos , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Administração Oral , Alcaloides/administração & dosagem , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Anticorpos/imunologia , Comportamento Animal/efeitos dos fármacos , Carbamatos/administração & dosagem , Inibidores da Colinesterase/administração & dosagem , Donepezila , Imuno-Histoquímica , Indanos/administração & dosagem , Injeções Intraperitoneais , Camundongos , Camundongos Transgênicos , Degeneração Neural/prevenção & controle , Fosforilação/efeitos dos fármacos , Piperidinas/administração & dosagem , Proteínas tau/metabolismoRESUMO
Cerebral deposition of beta-amyloid (Abeta) is an invariant event of Alzheimer's disease (AD). We recently described that the brain of aged transgenic mice expressing anti-nerve growth factor (NGF) antibodies (AD11 mice) show a dramatic neurodegenerative phenotype, reminiscent of AD, which includes neuronal loss, cholinergic deficit, and tau hyperphosphorylation, associated with neurofibrillary pathology. We now report that brains of aged transgenic mice contain large amounts of beta-amyloid plaques and describe their morphology by a variety of approaches. In conclusion, the chronic deprivation of NGF leads to the formation and deposition of Abeta in AD11 mice, suggesting a direct link between NGF signaling and abnormal processing of amyloid precursor protein.
Assuntos
Envelhecimento/genética , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Autoanticorpos/genética , Fator de Crescimento Neural/deficiência , Placa Amiloide/genética , Envelhecimento/imunologia , Envelhecimento/patologia , Doença de Alzheimer/imunologia , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Benzotiazóis , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/patologia , Cerebelo/imunologia , Cerebelo/metabolismo , Cerebelo/patologia , Modelos Animais de Doenças , Locus Cerúleo/imunologia , Locus Cerúleo/metabolismo , Locus Cerúleo/patologia , Camundongos , Camundongos Transgênicos , Neostriado/imunologia , Neostriado/metabolismo , Neostriado/patologia , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Emaranhados Neurofibrilares/metabolismo , Neurônios/imunologia , Neurônios/metabolismo , Neurônios/patologia , Placa Amiloide/imunologia , Placa Amiloide/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Coloração pela Prata , TiazóisRESUMO
Phenotypic knockout of nerve growth factor (NGF) activity in transgenic anti-NGF mice (AD11 mice) results in a progressive neurodegenerative phenotype resembling Alzheimer's disease. In this article, we examine whether and how the progressive neurodegenerative phenotype of AD11 mice could be prevented or ameliorated by pharmacological treatments with NGF or the cholinergic agonist galantamine, at a relatively early phase of Alzheimer's disease-like neurodegeneration. We demonstrate that the neurodegeneration induced by the expression of anti-NGF antibodies in AD11 mice can be largely reversed by NGF delivery through an olfactory route.