RT Journal Article
SR Electronic
T1 Age-linked suppression of lipoxin A4 mediates cognitive deficits in mice and humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.12.468379
DO 10.1101/2021.11.12.468379
A1 Fabricio A. Pamplona
A1 Gabriela Vitória
A1 Felipe C. Ribeiro
A1 Carolina A. Moraes
A1 Pitia Flores Ledur
A1 Karina Karmirian
A1 Isis M. Ornelas
A1 Luciana M. Leo
A1 Bruna Paulsen
A1 Felipe K. Sudo
A1 Gabriel Coutinho
A1 Claudia Drummond
A1 Naima Assunção
A1 Bart Vanderborght
A1 Claudio Canetti
A1 Hugo C. Castro-Faria-Neto
A1 Paulo Mattos
A1 Sergio T. Ferreira
A1 Stevens K. Rehen
A1 Fernando A. Bozza
A1 Mychael V. Lourenco
A1 Fernanda Tovar-Moll
YR 2021
UL http://biorxiv.org/content/early/2021/11/13/2021.11.12.468379.abstract
AB 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-α. 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.Competing Interest StatementThe authors have declared no competing interest.