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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2023.tde-10102023-112050
Document
Author
Full name
Caio Fábio Baêta Lopes
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2023
Supervisor
Committee
Alberici, Luciane Carla (President)
Ferrari, Merari de Fatima Ramires
Porcionatto, Marimelia Aparecida
Sebollela, Adriano Silva
Title in English
Drosophila melanogaster primary cell cultures as tools for neurobiology: focusing on mitochondria and Alzheimer's disease
Keywords in English
Alzheimer's disease
Drosophila melanogaster
Mitochondria
Mitophagy
Neuronal cultures
Abstract in English
Brains are the most complex known objects of universe. Such a complexity emerges from structure and connectivity between neurons, their main building blocks. These are high polarized cells, shaped to capture, to process and to convey electrical stimuli via synapses, orchestrating uncountable discrete signals that give rise to sophisticated phenomena, as consciousness. Neurodegenerative diseases are a set of devastating brain affections that course with neuronal senescence and death. Alzheimer's disease (AD), the leading cause of senile dementia worldwide, is a neurodegenerative disease characterized by progessive loss of cogniton and higher functions, due to diffuse central neurotoxicity, putatively attributed to senile plaques, composed of toxic amyloid peptides. Here I introduce a new, innovative, in vitro model for AD, based on third instar Drosophila melanogaster larval brains. The model proved adequate for live cell imaging, using fluorescent probes that allowed membrane, nuclear, mitochondrial and lysosomal stainings. Moreover, results obtained were robust and reproducible. Morphometric data indicate that amyloid missexpression in neurons lead to distinct structural phenotypes on the observed cells, leveraging potential uses of the model.
Title in Portuguese
Cultivos celulares primários de Drosophila melanogaster como ferramentas em neurobiologia: foco em mitocôndrias e doença de Alzheimer
Keywords in Portuguese
Culturas neuronais
Doença de Alzheimer
Drosophila melanogaster
Mitocôndria
Mitofagia
Abstract in Portuguese
Cérebros são os objetos mais complexos do universo conhecido. Tal complexidade emerge da estrutura e conectividade entre neurônios, as suas principais células. Estes são altamente polarizados, moldados para captar, processar e transmitir estímulos elétricos através das sinapses, orquestrando inúmeros sinais discretos que dão origem a fenômenos sofisticados, como a consciência. As doenças neurodegenerativas são um conjunto de afecções cerebrais devastadoras que cursam com senescência e morte neuronal. A doença de Alzheimer (DA), a principal causa de demência senil em todo o mundo, é uma doença neurodegenerativa caracterizada por uma perda progressiva da cognição e das funções superiores, devido a uma neurotoxicidade central difusa, putativamente atribuída a placas senis, compostas por peptídeos amilóides altamente tóxicos. Aqui apresento um novo e inovador modelo in vitro para a DA, baseado em cérebros de larvas de Drosophila melanogaster de terceiro instar. O modelo revelou-se adequado para a obtenção de imagens de células vivas, utilizando sondas fluorescentes que permitiram a coloração de membranas, núcleos, mitocôndria e lisossomos. Além disso, os resultados obtidos foram robustos e reprodutíveis. Os dados morfométricos indicam que a expressão incorreta de amilóide nos neurônios conduz a fenótipos estruturais distintos nas células observadas, favorecendo o alcance do modelo.
 
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Release Date
2025-07-07
Publishing Date
2023-12-06
 
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