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Record W4302424689 · doi:10.1101/2022.10.04.510850

Astrocyte-Oligodendrocyte interaction regulates central nervous system regeneration

2022· preprint· en· W4302424689 on OpenAlexaff
Irene Molina-González, R. Holloway, Zoeb Jiwaji, Owen Dando, Katie Emelianova, Amy Lloyd, Lindsey H. Forbes, Ayisha Mahmood, Thomas Skripuletz, Viktoria Gudi, James A. Febery, Jeffrey A. Johnson, Jill H. Fowler, Tanja Kuhlmann, Anna Williams, Siddharthan Chandran, Martin Stangel, Andrew J.M. Howden, Giles E. Hardingham, Véronique E. Miron

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldNeuroscience
TopicNeurogenesis and neuroplasticity mechanisms
Canadian institutionsUniversity of TorontoSt. Michael's Hospital
FundersMedical Research CouncilMedizinischen Hochschule HannoverDeutsche ForschungsgemeinschaftMultiple Sclerosis Society
KeywordsRemyelinationAstrocyteOligodendrocyteCentral nervous systemRegeneration (biology)NeuroscienceMyelinAstrogliosisBiologyNeurogliaDownregulation and upregulationStimulationNervous systemCell biologyBiochemistry

Abstract

fetched live from OpenAlex

Summary Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand 1,2 . Here, we show that interaction between glial cells – astrocytes and mature myelin-forming oligodendrocytes – is a critical determinant of remyelination. Astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.

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 score0.002
Threshold uncertainty score0.005

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.224
Teacher spread0.201 · 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

Citations6
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicNeurogenesis and neuroplasticity mechanismsFrench-language works237,207