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Record W4311436859 · doi:10.1038/s41586-022-05534-y

Microglia regulate central nervous system myelin growth and integrity

2022· article· en· W4311436859 on OpenAlexaff
Niamh B. McNamara, David A. D. Munro, Nadine Bestard-Cuche, Akiko Uyeda, Jeroen F. J. Bogie, Alana Hoffmann, R. Holloway, Irene Molina-González, Katharine E. Askew, Stephen Mitchell, William Mungall, Michael Dodds, Carsten Dittmayer, Jonathan Moss, Jamie Rose, Stefan Szymkowiak, Lukas Amann, Barry W. McColl, Marco Prinz, Tara L. Spires‐Jones, Werner Stenzel, Karen Horsburgh, Jerome J. A. Hendriks, Clare Pridans, Rieko Muramatsu, Anna Williams, Josef Priller, Véronique E. Miron

Bibliographic record

VenueNature · 2022
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsToronto East General HospitalPublic Health OntarioUniversity of TorontoSt. Michael's Hospital
FundersMedical Research CouncilReta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology,University College LondonDirectorate for Biological SciencesFondation CharcotSimons Initiative for the Developing BrainUK Dementia Research InstituteVlaamse regeringUniversity of EdinburghWellcome TrustMultiple Sclerosis SocietyFonds Wetenschappelijk OnderzoekUniversity College London
KeywordsMyelinMicrogliaCentral nervous systemOligodendrocyteNeuroscienceBiologyMacrophageNeuroinflammationCell biologyImmunologyInflammationGeneticsIn vitro

Abstract

fetched live from OpenAlex

Abstract Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health 1 , it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1–TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease 2,3 .

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.078
Threshold uncertainty score0.916

Codex and Gemma teacher scores by category

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 integrity0.0000.002
Insufficient payload (model declined to judge)0.0000.000

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 head0.013
GPT teacher head0.232
Teacher spread0.218 · 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 teacher head, 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

Citations475
Published2022
Admission routes1
Has abstractyes

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