期刊
CELL REPORTS
卷 30, 期 7, 页码 2180-2194出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.01.072
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资金
- Human Frontiers Science Program (HFSP)
- John Simon Guggenheim Foundation
- National Institute for Translational Neuroscience (INNT/Brazil)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- CNPq
- FAPERJ
- LABEX (excellence laboratory, program investment for the future)
- DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease)
- Hospital University Federation (FHU) OncoAge
Obesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, and higher risk of developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate the effects of palmitate, a saturated fatty acid present at high amounts in fat-rich diets, in the brain. Palmitate is increased in the cerebrospinal fluid (CSF) of overweight and obese patients with amnestic mild cognitive impairment. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Palmitate induces astroglial and microglial activation in the mouse hippocampus, and its deleterious impact is mediated by microglia-derived tumor necrosis factor alpha (TNF-alpha) signaling. Our results establish that obesity is associated with increases in CSF palmitate. By defining a pro-inflammatory mechanism by which abnormal levels of palmitate in the brain impair memory, the results further suggest that anti-inflammatory strategies may attenuate memory impairment in obesity.
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