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1.
Dis Model Mech ; 7(3): 373-85, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24487408

RESUMO

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory loss and decreased synaptic function. Advances in transgenic animal models of AD have facilitated our understanding of this disorder, and have aided in the development, speed and efficiency of testing potential therapeutics. Recently, we have described the characterization of a novel model of AD in the fruit fly, Drosophila melanogaster, where we expressed the human AD-associated proteins APP and BACE in the central nervous system of the fly. Here we describe synaptic defects in the larval neuromuscular junction (NMJ) in this model. Our results indicate that expression of human APP and BACE at the larval NMJ leads to defective larval locomotion behavior, decreased presynaptic connections, altered mitochondrial localization in presynaptic motor neurons and decreased postsynaptic protein levels. Treating larvae expressing APP and BACE with the γ-secretase inhibitor L-685,458 suppresses the behavioral defects as well as the pre- and postsynaptic defects. We suggest that this model will be useful to assess and model the synaptic dysfunction normally associated with AD, and will also serve as a powerful in vivo tool for rapid testing of potential therapeutics for AD.


Assuntos
Doença de Alzheimer/patologia , Drosophila melanogaster/fisiologia , Sinapses/patologia , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Animais Geneticamente Modificados , Ácido Aspártico Endopeptidases/metabolismo , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Inibidores Enzimáticos/farmacologia , Humanos , Larva/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Fenótipo , Transporte Proteico/efeitos dos fármacos , Sinapses/metabolismo , Transgenes
3.
Med Teach ; 24(4): 412-6, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12193326

RESUMO

An interactive computer-assisted learning (CAL) module on glomerulonephritis, previously identified by fourth-year medical students as a difficult topic, was developed. The module comprised background material, case studies, graphics, animation, video and supporting quizzes with feedback. The impact of the module on student learning was evaluated by comparing the performance of two matched groups of students, only one of which accessed the CAL module, in an online assessment. The analysis examined the effect of having completed a clinical term in renal medicine. A significant improvement in the performance of those students who used the CAL module was demonstrated. Unexpectedly, completing a renal medicine term had no beneficial influence on students' performance. Students who used the CAL module perceived a significant decrease in the difficulty of the topic. It is concluded that the module is an effective learning tool, but important caveats are noted associated with using CAL modules in redesigned medical curricula.


Assuntos
Instrução por Computador , Educação de Graduação em Medicina/métodos , Glomerulonefrite/patologia , Aprendizagem , Currículo , Retroalimentação , Humanos , New South Wales , Desenvolvimento de Programas , Estudantes de Medicina , Inquéritos e Questionários
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