Age-linked suppression of lipoxin A4 associates with cognitive deficits in mice and humans.

Autor: Pamplona FA; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. fabriciopamplona@gmail.com.; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. fabriciopamplona@gmail.com.; Biosciences Program, Federal University for Latin American Integration, Foz do Iguaçu, Brazil. fabriciopamplona@gmail.com., Vitória G; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Sudo FK; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Ribeiro FC; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil., Isaac AR; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil., Moraes CA; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil., Chauvet MG; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil., Ledur PF; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Karmirian K; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.; Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil., Ornelas IM; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.; Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, 29040-090, Brazil., Leo LM; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil., Paulsen B; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02141, USA., Coutinho G; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Drummond C; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.; Department of Speech and Hearing Pathology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil., Assunção N; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Vanderborght B; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Canetti CA; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil., Castro-Faria-Neto HC; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil., Mattos P; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Ferreira ST; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil., Rehen SK; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.; Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil., Bozza FA; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil., Lourenco MV; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil. mychael@bioqmed.ufrj.br., Tovar-Moll F; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil. fernanda.tovarmoll@idor.org.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2022 Oct 10; Vol. 12 (1), pp. 439. Date of Electronic Publication: 2022 Oct 10.
DOI: 10.1038/s41398-022-02208-1
Abstrakt: 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 associated with cognitive 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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