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Record W2971572266 · doi:10.1101/744136

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

2019· preprint· en· W2971572266 on OpenAlexafffund
Charlotte Madore, Quentin Leyrolle, Lydie Morel, Jean-Christophe Delpech, Andrew D. Greenhalgh, Chloé Lacabanne, Clémentine Bosch‐Bouju, Julien Bourel, Aurore Thomazeau, Kathryn E. Hopperton, Sol Beccari, A. Séré, Agnès Aubert, Véronique De Smedt‐Peyrusse, Cynthia Lecours, Kanchan Bisht, Lawrence Fourgeaud, Stéphane Gregoire, Lionel Brétillon, Nancy J. Grant, Jérôme Badaut, Pierre Gressèns, Amanda Sierra, Oleg Butovsky, Marie‐Ève Tremblay, Richard P. Bazinet, Agnès Nadjar, Sophie Layé

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldNursing
TopicFatty Acid Research and Health
Canadian institutionsUniversité LavalUniversity of Toronto
FundersCentre National de la Recherche ScientifiqueMinisterio de Economía y CompetitividadBanco Bilbao Vizcaya ArgentariaEusko JaurlaritzaCHIST-ERAAgence Nationale de la RechercheInstitut National de la Recherche AgronomiqueFondation pour la Recherche MédicaleInstitut National de la Santé et de la Recherche MédicaleNational Alliance for Research on Schizophrenia and DepressionHospital for Sick ChildrenCanadian Institutes of Health ResearchUniversité de ParisFundación BBVA
KeywordsPolyunsaturated fatty acidOffspringMicrogliaBiologySynapseHippocampal formationNeuroscienceEndocrinologyInternal medicineBiochemistryMedicineImmunologyFatty acidPregnancyInflammationGenetics

Abstract

fetched live from OpenAlex

SUMMARY Omega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in epidemiological studies, but the mechanisms by which a n-3 PUFA dietary imbalance affects CNS development are poorly understood. Active microglial engulfment of synaptic elements is an important process for normal brain development and altered synapse refinement is a hallmark of several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development. Our results show that maternal dietary n-3 PUFA deficiency increases microglial phagocytosis of synaptic elements in the developing hippocampus, through the activation of 12/15- lipoxygenase (LOX)/12-HETE signaling, which alters neuronal morphology and affects cognition in the postnatal offspring. While women of child bearing age are at higher risk of dietary n-3 PUFA deficiency, these findings provide new insights into the mechanisms linking maternal nutrition to neurodevelopmental disorders. One Sentence Summary Low maternal omega-3 fatty acids intake impairs microglia-mediated synaptic refinement via 12-HETE pathway in the developing brain.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.027

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0080.003

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 head0.022
GPT teacher head0.283
Teacher spread0.261 · 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 designBench or experimental
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

Citations3
Published2019
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicFatty Acid Research and Health→French-language works237,207→