Título:	Efeitos de diferentes estatinas sobre micróglias, neurônios e a resposta à infecção pelo vírus Zika
Autor(es):	Calixto, Gabriel Felipe Gomes
Orientador(es):	Magalhães, Kelly Grace
Assunto:	Estatinas Colesterol Micróglia Zika vírus Efeitos adversos
Data de publicação:	3-Mar-2026
Data de defesa:	11-Mar-2025
Referência:	CALIXTO, Gabriel Felipe Gomes. Efeitos de diferentes estatinas sobre micróglias, neurônios e a resposta à infecção pelo vírus Zika. 2025. 106 f., il. Dissertação (Mestrado em Biologia Molecular) — Universidade de Brasília, Brasília, 2025.
Abstract:	Statins are among the most widely used drugs worldwide due to their ability to reduce low-density lipoprotein (LDL), preventing and treating cardiovascular diseases. Although their benefits outweigh the risks in most cases, adverse effects are common, especially with lipophilic statins. These effects include muscular and hepatic manifestations, as well as alterations in the central nervous system (CNS). The lack of a satisfactory explanation for these neurological effects highlights the importance of investigations in relevant models, such as microglia and neurons, which play central roles in the CNS. Additionally, the ability of statins to reduce cholesterol synthesis is not only studied in the prevention of cardiovascular diseases but also in other pathological contexts. Lipid metabolism is crucial in infections caused by viruses of the Orthoflavivirus genus, such as Zika virus (ZIKV), which often induces an increase in cholesterol synthesis and uptake. At the same time, cholesterol reduction has demonstrated antiviral effects, emphasizing the role of this molecule in infection. Considering that the brain is the richest organ in cholesterol and that ZIKV exhibits neurological tropism—illustrated by congenital complications in children born to infected mothers—the potential benefits of statin use in this infection remain an open question. Thus, the present study aims to evaluate the effects of different statins on microglia and neurons, as well as their influence on the response to ZIKV infection. To achieve this, microglial cells (C20) and neurons were treated with lipophilic or hydrophilic statins for different periods to analyze cytotoxicity, inflammation, and cell death. Moreover, we assessed the metabolic profile and modulation of the mevalonate pathway during ZIKV infection in microglial cells. We also treated these cells with statins before and during the infection to investigate cytotoxicity, the generation of reactive oxygen species (ROS), and viral load. We identified that lipophilic statins increase cytotoxicity and cell death compared to hydrophilic statins, both in microglia and neurons. In microglia, this cytotoxicity was independent of ROS at early time points and was accompanied by a more pro-inflammatory phenotype in lipophilic statins. We observed an increase in mevalonate pathway products during microglial infection with ZIKV, including cholesterol and isoprenoids. Furthermore, treatment with rosuvastatin reduced oxidative stress in infected cells and prevented ZIKV-induced microglial viability loss without altering viral load. These findings provide valuable insights into the possible mechanisms underlying neurological adverse effects associated with statin use, as well as the identification of potential targets for more effective therapeutic interventions against ZIKV.
Unidade Acadêmica:	Instituto de Ciências Biológicas (IB) Departamento de Biologia Celular (IB CEL)
Informações adicionais:	Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Biologia Celular, Programa de Pós-Graduação em Biologia Molecular, 2025.
Programa de pós-graduação:	Programa de Pós-Graduação em Biologia Molecular
Licença:	A concessão da licença deste item refere-se ao termo de autorização impresso assinado pelo autor com as seguintes condições: Na qualidade de titular dos direitos de autor da publicação, autorizo a Universidade de Brasília e o IBICT a disponibilizar por meio dos sites www.unb.br, www.ibict.br, www.ndltd.org sem ressarcimento dos direitos autorais, de acordo com a Lei nº 9610/98, o texto integral da obra supracitada, conforme permissões assinaladas, para fins de leitura, impressão e/ou download, a título de divulgação da produção científica brasileira, a partir desta data.
Agência financiadora:	Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico, Tecnológico (CNPq) e Fundação de Apoio à Pesquisa do Distrito Federal (FAP/DF) e FINEP.
Aparece nas coleções:	Teses, dissertações e produtos pós-doutorado

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