| Author | Duarte-Silva, Eduardo | |
| Author | Araújo, Shyrlene Meiry da Rocha | |
| Author | Oliveira, Wilma Helena | |
| Author | Lós, Deniele Bezerra | |
| Author | Bonfanti, Amanda Pires | |
| Author | Peron, Gabriela | |
| Author | Thomaz, Livia de Lima | |
| Author | Verinaud, Liana | |
| Author | Peixoto, Christina Alves | |
| Access date | 2025-05-12T01:46:14Z | |
| Available date | 2025-05-12T01:46:14Z | |
| Document date | 2021 | |
| Citation | DUARTE-SILVA, Eduardo et al. Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord. v. 12, p. 1-11, May 2021. | en_US |
| ISSN | 1664-3224 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/70351 | |
| Sponsorship | The authors express their gratitude to Oswaldo Cruz Foundation of Pernambuco (FIOCRUZ-PE), Research Excellence Program - Aggeu Magalhães Institute (IAM PROEP#400208/2019-9), Knowledge Generation Program – Oswaldo Cruz Foundation (FIOCRUZ; #VPPCB-007-FIO-18-2-17), The Brazilian National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM; #465489/2014-1), and Brazilian National Council for Scientific and Technological Development (CNPq; #301777/2012-8) for research support. This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nıvel Superior - ́Brasil (CAPES) - Finance Code 001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | en_US |
| Language | eng | en_US |
| Publisher | Frontiers Research Foundation | en_US |
| Rights | open access | en_US |
| Title | Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord | en_US |
| Type | Article | en_US |
| DOI | 10.3389/fimmu.2021.671511 | |
| Abstract | Multiple Sclerosis (MS) is a neuroinflammatory and chronic Central Nervous System (CNS) disease that affects millions of people worldwide. The search for more promising drugs for the treatment of MS has led to studies on Sildenafil, a phosphodiesterase type 5 Inhibitor (PDE5I) that has been shown to possess neuroprotective effects in the Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS. We have previously shown that Sildenafil improves the clinical score of EAE mice via modulation of apoptotic pathways, but other signaling pathways were not previously covered. Therefore, the aim of the present study was to further investigate the effects of Sildenafil treatment on autophagy and nitrosative stress signaling pathways in EAE. 24 female C57BL/6 mice were divided into the following groups: (A) Control - received only water; (B) EAE - EAE untreated mice; (C) SILD - EAE mice treated with 25mg/kg of Sildenafil s.c. The results showed that EAE mice presented a pro-nitrosative profile characterized by high tissue nitrite levels, lowered levels of p-eNOS and high levels of iNOS. Furthermore, decreased levels of LC3, beclin-1 and ATG5, suggests impaired autophagy, and decreased levels of AMPK in the spinal cord were also detected in EAE mice. Surprisingly, treatment with Sildenafil inhibited nitrosative stress and augmented the levels of LC3, beclin-1, ATG5, p-CREB and BDNF and decreased mTOR levels, as well as augmented p-AMPK. In conclusion, we propose that Sildenafil alleviates EAE by activating autophagy via the eNOS-NO-AMPK-mTOR-LC3-beclin1-ATG5 and eNOS-NO-AMPK-mTOR-CREB-BDNF pathways in the spinal cord. | en_US |
| Affilliation | Oswaldo Cruz Foundation. Aggeu Magalhães Institute. Laboratory of Ultrastructure. Recife, PE, Brazil / Oswaldo Cruz Foundation. Aggeu Magalhães Institute. Postgraduate Program in Biosciences and Biotechnology for Health. Recife, PE, Brazil / Universal Scientific Education and Research Network. Malignancy and Autoimmunity. Network of Immunity in Infection. Recife, PE, Brazil. | en_US |
| Affilliation | Oswaldo Cruz Foundation. Aggeu Magalhães Institute. Laboratory of Ultrastructure. Recife, PE, Brazil / Federal University of Pernambuco. Postgraduate Program in Biological Sciences/Center of Biosciences. Recife, PE, Brazil. | en_US |
| Affilliation | Oswaldo Cruz Foundation. Aggeu Magalhães Institute. Laboratory of Ultrastructure. Recife, PE, Brazil / Federal University of Pernambuco. Postgraduate Program in Biological Sciences/Center of Biosciences. Recife, PE, Brazil. | en_US |
| Affilliation | Federal University of Pernambuco. Postgraduate Program in Biotechnology/Northeast Network in Biotechnology. Recife, PE, Brazil. | en_US |
| Affilliation | University of Campinas. Department of Structural and Functional Biology. Campinas, SP, Brazil. | en_US |
| Affilliation | University of Campinas. Department of Structural and Functional Biology. Campinas, SP, Brazil. | en_US |
| Affilliation | University of Campinas. Department of Structural and Functional Biology. Campinas, SP, Brazil. | en_US |
| Affilliation | University of Campinas. Department of Structural and Functional Biology. Campinas, SP, Brazil. | en_US |
| Affilliation | Oswaldo Cruz Foundation. Aggeu Magalhães Institute. Laboratory of Ultrastructure. Recife, PE, Brazil / Oswaldo Cruz Foundation. Oswaldo Cruz Institute. National Institute of Science and Technology on Neuroimmunomodulation. Rio de Janeiro, RJ, Brasil. | en_US |
| Subject | EAE (Experimental Autoimmune Encephalomyelitis) | en_US |
| Subject | Sildenafil citrate (Viagra) | en_US |
| Subject | Neuroinflammation | en_US |
| Subject | Autophagy | en_US |
| Subject | Nitrosative stress | en_US |
| e-ISSN | 1664-3224 | |
