| Author | Duarte-Silva, Eduardo | |
| Author | Araújo, Shyrlene Meiry da Rocha | |
| Author | Oliveira, Wilma Helena | |
| Author | Lós, Deniele Bezerra de | |
| Author | França, Maria Eduarda Rocha de | |
| Author | Bonfanti, Amanda Pires | |
| Author | Peron, Gabriela | |
| Author | Thomaz, Livia de Lima | |
| Author | Verinaud, Liana | |
| Author | Nunes, Ana Karolina de Santana | |
| Author | Peixoto, Christina Alves | |
| Access date | 2019-11-12T14:31:54Z | |
| Available date | 2019-11-12T14:31:54Z | |
| Document date | 2018 | |
| Citation | DUARTE-SILVA, Eduardo et al. Sildenafil ameliorates EAE by decreasing apoptosis in the spinal cord of C57BL/6 mice. Journal of Neuroimmunology, v. 321, p. 125-137, 2018. | pt_BR |
| ISSN | 0165-5728 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/37006 | |
| Sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Fundação de Amparo à Ciência e Tecnologia de Estado de Pernambuco (FACEPE)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) | pt_BR |
| Language | eng | pt_BR |
| Rights | restricted access | pt_BR |
| Title | Sildenafil ameliorates EAE by decreasing apoptosis in the spinal cord of C57BL/6 mice | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.jneuroim.2018.06.002 | |
| Abstract | Apoptosis is one form of cell death that is intimately related to health and pathological conditions. In most neuroinflammatory and/or neurodegenerative diseases, apoptosis is associated with disease development and pathology and inhibition of this process leads to considerable amelioration. It is becoming evident that apoptosis also participates in the pathogenesis of Multiple Sclerosis (MS) and its animal model, Experimental Autoimmune Encephalomyelitis (EAE). Drugs such as Sildenafil, a Phosphodiesterase type 5 Inhibitor (PDE5I), have proven to be neuroprotective in MS models. However, it is not known whether Sildenafil is able to modulate cell death, specifically apoptosis, in EAE mice. Therefore, the aim of this study was to determine the effects of Sildenafil on extrinsic and intrinsic apoptosis pathways in the spinal cord of C57BL/6 mice with EAE. TUNEL analysis showed that EAE mice had elevated number of TUNEL+ cells and that treatment with Sildenafil led to reduced number of dying cells, indicating that Sildenafil was able to inhibit cell death. We observed that both extrinsic and intrinsic pathways of apoptosis were governing the dynamics of EAE progression. We showed that in EAE mice there were increased levels of extrinsic (Caspase-8, -3, TNF-α, FADD) and intrinsic (Caspase-9, Bax and Cytochrome C) apoptosis markers. Bcl-2, an anti-apoptotic protein, was downregulated in EAE mice. We also demonstrated that EAE mice had increased levels of non-caspase mediators of cell survival/cell death (p-IκBα and p-MAPK-p38). Besides, EAE mice presented augmented demyelination. Nevertheless, this is the first research to demonstrate that Sildenafil, when administered concomitant to disease induction, modulated the expression of pro- and anti-apoptotic proteins of the extrinsic and intrinsic pathways, as well as diminished the expression of non-caspase mediators and promoted remyelination in the spinal cord, indicating neuroprotective effects. Thus, the present study demonstrated that Sildenafil inhibits apoptosis by two distinct, although interconnected, mechanisms: directly by modulating caspase expression (through extrinsic and intrinsic pathways) and indirectly by modulating the expression of molecules involved in cell death and/or cell survival. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Ultraestrutura. Recife, PE, Brasil; Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Programa de Pós-Graduação em Biociências e Biotecnologia para a Saúde. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Ultraestrutura. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Ultraestrutura. Recife, PE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Programa de Pós-Graduação em Biotecnologia / Rede Nordeste de Biotecnologia. Recife, PE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Centro de Biociências Programa de Pós-Graduação em Ciências Biológicas. Recife, PE, Brasil. | pt_BR |
| Affilliation | Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Campinas, SP, Brasil. | pt_BR |
| Affilliation | Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Campinas, SP, Brasil. | pt_BR |
| Affilliation | Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Campinas, SP, Brasil. | pt_BR |
| Affilliation | Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Campinas, SP, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Centro de Biociências Programa de Pós-Graduação em Ciências Biológicas. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Ultraestrutura. Recife, PE, Brasil / Instituto de Ciência e Tecnologia em Neuroimunomodulação. Recife, PE, Brasil. | pt_BR |
| Subject | Apoptosis | pt_BR |
| Subject | C57BL/6 mice | pt_BR |
| Subject | EAE | pt_BR |
| Subject | MS | pt_BR |
| Subject | Remyelination | pt_BR |
| Subject | Sildenafil | pt_BR |
| DeCS | Animais | pt_BR |
| DeCS | Apoptose / efeitos dos fármacos | pt_BR |
| DeCS | Apoptosis / fisiologia | pt_BR |
| DeCS | Encefalomielite Autoimune Experimental / Tratamento Farmacológico | pt_BR |
| DeCS | Encefalomielite Autoimune Experimental / imunologia | pt_BR |
| DeCS | Encefalomielite Autoimune Experimental / patologia | pt_BR |
| DeCS | Feminino | pt_BR |
| DeCS | Camundongos | pt_BR |
| DeCS | Camundongos Endogâmicos C57BL | pt_BR |
| DeCS | Técnicas de Cultura de Órgãos | pt_BR |
| DeCS | Inibidores da Fosfodiesterase 5 / farmacologia | pt_BR |
| DeCS | Inibidores da Fosfodiesterase 5 / uso terapêutico | pt_BR |
| DeCS | Citrato de Sildenafila / farmacologia | pt_BR |
| DeCS | Citrato de Sildenafila / uso terapêutico | pt_BR |
| DeCS | Medula Espinal / efeitos dos fármacos | pt_BR |
| DeCS | Medula Espinal / imunologia | pt_BR |
| DeCS | Medula Espinal / patologia | pt_BR |
| e-ISSN | 0165-5728 | |
| Embargo date | 2050-01-01 | |
