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Record W3007137838 · doi:10.1016/j.celrep.2020.01.072

Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α

2020· article· en· W3007137838 on OpenAlexaff
Helen M. Melo, Gisele da S. Seixas da Silva, Marcella Ramos Sant’Ana, Camila Vieira Ligo Teixeira, Julia R. Clarke, Vivian S. M. Coreixas, Bruno C. de Melo, Juliana T.S. Fortuna, Letícia Forny‐Germano, José Henrique Ledo, Maira Souza Oliveira Barreto, Cláudia P. Figueiredo, Raphaëlle Pardossi‐Piquard, Frédéric Checler, José M. Delgado‐García, Agnès Gruart, Lı́cio A. Velloso, Márcio Luiz Figueredo Balthazar, Dennys E. Cintra, Sérgio T. Ferreira, Fernanda G. De Felice

Bibliographic record

VenueCell Reports · 2020
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsQueen's University
FundersInstitute for Translational NeuroscienceFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de JaneiroConselho Nacional de Desenvolvimento Científico e TecnológicoLabexUniversidade Federal do Rio de JaneiroAgence Nationale de la RechercheHuman Frontier Science ProgramJohn Simon Guggenheim Memorial Foundation
KeywordsMicrogliaHippocampusCerebrospinal fluidEndocrinologySynaptic plasticityInternal medicineTumor necrosis factor alphaMedicineMorris water navigation taskCognitive declineMemory impairmentInflammationDementiaAtrophyNeurosciencePsychologyCognitionReceptorDisease

Abstract

fetched live from OpenAlex

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-α) 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.227
Teacher spread0.203 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations142
Published2020
Admission routes1
Has abstractyes

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