Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/55245 |
Resumo: | Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal da Integração Latino-Americana. Foz do Iguaçu, PR, Brasil. |
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Pamplona, Fabricio A.Vitória, GabrielaRibeiro, Felipe C.Moraes, Carolina A.Ledur, Pitia FloresKarmirian, KarinaOrnelas, Isis M.Leo, Luciana M.Paulsen, BrunaSudo, Felipe K.Coutinho, GabrielDrummond, ClaudiaAssunção, NaimaVanderborght, BartCanetti, ClaudioFaria Neto, Hugo Caire CastroMattos, PauloFerreira, Sergio T.Rehen, Stevens K.Bozza, Fernando A.Lourenço, Mychael V.Tovar-Moll, Fernanda2022-10-23T14:25:42Z2022-10-23T14:25:42Z2021PAMPLONA, Fabricio A. et al. Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans. bioRxiv, p. 1-36, Nov. 2021.https://www.arca.fiocruz.br/handle/icict/5524510.1101/2021.11.12.468379engbioRxiv preprintLIPOxina A4Sinalização endocanabinóideMemóriaEnvelhecimentoDoença de AlzheimerLipoxin A4Endocannabinoid signalingMemoryAgingAlzheimer's diseaseAge-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humansLipoxin and memory in aging and Alzheimer's diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleInstituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal da Integração Latino-Americana. Foz do Iguaçu, PR, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Harvard University. Department of Stem Cell and Regenerative Biology. Cambridge, MA, USA / Broad Institute of MIT and Harvard. Stanley Center for Psychiatric Research. Cambridge, MA, USA.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Faculdade de Medicina. Departamento de Fonoaudiologia. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Psiquiatria. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer’s disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system. We demonstrate that genetic suppression of 5-lipoxygenase (5-LOX), the enzyme mediating LXA4 synthesis, promotes learning impairment in mice. Conversely, administration of exogenous LXA4 attenuated cytokine production and memory loss induced by inflammation in mice. We further show that cerebrospinal fluid LXA4 is reduced in patients with dementia and positively associates with memory performance, brain-derived neurotrophic factor (BDNF), and AD-linked amyloid-β. Our findings suggest that reduced LXA4 levels may lead to vulnerability to age-related cognitive disorders and that promoting LXA4 signaling may comprise an effective strategy to prevent early cognitive decline in AD.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALFabricioPamplona_LucianaMLeo_etal_IOC_2022.pdfFabricioPamplona_LucianaMLeo_etal_IOC_2022.pdfapplication/pdf2658981https://www.arca.fiocruz.br/bitstream/icict/55245/2/FabricioPamplona_LucianaMLeo_etal_IOC_2022.pdfc77c1665297f0a2f0d207a2f09876583MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/55245/1/license.txt5a560609d32a3863062d77ff32785d58MD51icict/552452022-11-23 21:13:44.628oai:www.arca.fiocruz.br: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ório 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| dc.title.en_US.fl_str_mv |
Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans |
| dc.title.alternative.en_US.fl_str_mv |
Lipoxin and memory in aging and Alzheimer's disease |
| title |
Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans |
| spellingShingle |
Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans Pamplona, Fabricio A. LIPOxina A4 Sinalização endocanabinóide Memória Envelhecimento Doença de Alzheimer Lipoxin A4 Endocannabinoid signaling Memory Aging Alzheimer's disease |
| title_short |
Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans |
| title_full |
Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans |
| title_fullStr |
Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans |
| title_full_unstemmed |
Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans |
| title_sort |
Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans |
| author |
Pamplona, Fabricio A. |
| author_facet |
Pamplona, Fabricio A. Vitória, Gabriela Ribeiro, Felipe C. Moraes, Carolina A. Ledur, Pitia Flores Karmirian, Karina Ornelas, Isis M. Leo, Luciana M. Paulsen, Bruna Sudo, Felipe K. Coutinho, Gabriel Drummond, Claudia Assunção, Naima Vanderborght, Bart Canetti, Claudio Faria Neto, Hugo Caire Castro Mattos, Paulo Ferreira, Sergio T. Rehen, Stevens K. Bozza, Fernando A. Lourenço, Mychael V. Tovar-Moll, Fernanda |
| author_role |
author |
| author2 |
Vitória, Gabriela Ribeiro, Felipe C. Moraes, Carolina A. Ledur, Pitia Flores Karmirian, Karina Ornelas, Isis M. Leo, Luciana M. Paulsen, Bruna Sudo, Felipe K. Coutinho, Gabriel Drummond, Claudia Assunção, Naima Vanderborght, Bart Canetti, Claudio Faria Neto, Hugo Caire Castro Mattos, Paulo Ferreira, Sergio T. Rehen, Stevens K. Bozza, Fernando A. Lourenço, Mychael V. Tovar-Moll, Fernanda |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Pamplona, Fabricio A. Vitória, Gabriela Ribeiro, Felipe C. Moraes, Carolina A. Ledur, Pitia Flores Karmirian, Karina Ornelas, Isis M. Leo, Luciana M. Paulsen, Bruna Sudo, Felipe K. Coutinho, Gabriel Drummond, Claudia Assunção, Naima Vanderborght, Bart Canetti, Claudio Faria Neto, Hugo Caire Castro Mattos, Paulo Ferreira, Sergio T. Rehen, Stevens K. Bozza, Fernando A. Lourenço, Mychael V. Tovar-Moll, Fernanda |
| dc.subject.other.en_US.fl_str_mv |
LIPOxina A4 Sinalização endocanabinóide Memória Envelhecimento Doença de Alzheimer |
| topic |
LIPOxina A4 Sinalização endocanabinóide Memória Envelhecimento Doença de Alzheimer Lipoxin A4 Endocannabinoid signaling Memory Aging Alzheimer's disease |
| dc.subject.en.en_US.fl_str_mv |
Lipoxin A4 Endocannabinoid signaling Memory Aging Alzheimer's disease |
| description |
Instituto D'Or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal da Integração Latino-Americana. Foz do Iguaçu, PR, Brasil. |
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2021 |
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2021 |
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2022-10-23T14:25:42Z |
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2022-10-23T14:25:42Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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PAMPLONA, Fabricio A. et al. Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans. bioRxiv, p. 1-36, Nov. 2021. |
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https://www.arca.fiocruz.br/handle/icict/55245 |
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10.1101/2021.11.12.468379 |
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PAMPLONA, Fabricio A. et al. Age-linked suppression of lipoxin A4 medi 1 ates cognitive deficits in mice and humans. bioRxiv, p. 1-36, Nov. 2021. 10.1101/2021.11.12.468379 |
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bioRxiv preprint |
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bioRxiv preprint |
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