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Record W4400779419 · doi:10.1002/glia.24589

<i>Myelin basic protein</i> mRNA levels affect myelin sheath dimensions, architecture, plasticity, and density of resident glial cells

2024· article· en· W4400779419 on OpenAlexafffund
Hooman Bagheri, Hana Friedman, Amanda Hadwen, Celia Jarweh, Ellis Cooper, Lawrence Oprea, Claire Guerrier, Anmar Khadra, A. Collin, Julien Cohen‐Adad, Amanda Young, Gerardo Mendez Victoriano, Matthew Swire, Andrew A. Jarjour, Marie E. Bechler, Rachel S. Pryce, Pierre Chaurand, Lise Cougnaud, Dajana Vuckovic, Elliott M Wilion, Owen Greene, Akiko Nishiyama, Anouk Benmamar‐Badel, Trevor Owens, Vladimir Grouza, Marius Tuznik, Hanwen Liu, David A. Rudko, Jinyi Zhang, Katherine A. Siminovitch, Alan C. Peterson

Bibliographic record

VenueGlia · 2024
Typearticle
Languageen
FieldNeuroscience
TopicNeurogenesis and neuroplasticity mechanisms
Canadian institutionsLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalToronto General HospitalUniversity of TorontoMontreal Neurological Institute and HospitalPolytechnique MontréalConcordia UniversityUniversité de MontréalMcGill University
FundersNational Institute of Neurological Disorders and StrokeMedical Research CouncilFonds de Recherche du Québec - SantéNational Institutes of HealthCanada First Research Excellence FundNatural Sciences and Engineering Research Council of CanadaMcGill UniversityUniversity of Connecticut
KeywordsBiologyMyelinMyelin basic proteinNeuroscienceAffect (linguistics)Myelin sheathNeuroplasticityCell biologyCentral nervous systemCommunicationPsychology

Abstract

fetched live from OpenAlex

Myelin Basic Protein (MBP) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyelination. How different Mbp mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer-edited mouse lines that accumulate Mbp mRNA levels ranging from 8% to 160% of wild type. In young mice, reduced Mbp mRNA levels resulted in corresponding decreases in Mbp protein accumulation and myelin sheath thickness, confirming the previously demonstrated rate-limiting role of Mbp transcription in the control of initial myelin synthesis. However, despite maintaining lower line specific Mbp mRNA levels into old age, both MBP protein levels and myelin thickness improved or fully normalized at rates defined by the relative Mbp mRNA level. Sheath length, in contrast, was affected only when mRNA levels were very low, demonstrating that sheath thickness and length are not equally coupled to Mbp mRNA level. Striking abnormalities in sheath structure also emerged with reduced mRNA levels. Unexpectedly, an increase in the density of all glial cell types arose in response to reduced Mbp mRNA levels. This investigation extends understanding of the role MBP plays in myelin sheath elaboration, architecture, and plasticity across the mouse lifespan and illuminates a novel axis of glial cell crosstalk.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.003
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
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)0.0000.000

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 head0.028
GPT teacher head0.253
Teacher spread0.226 · 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.

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

Citations22
Published2024
Admission routes2
Has abstractyes

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