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Record W4413037002 · doi:10.1101/2025.08.06.668920

Spared cognitive and social function following perinatal ablation of ATRX despite transient microglia dysregulation

2025· preprint· en· W4413037002 on OpenAlexafffund
Sarfraz Shafiq, Nathalie G. Bérubé

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsChildren’s Health Research InstituteWestern University
FundersCanadian Institutes of Health Research
KeywordsMicrogliaTransient (computer programming)NeuroscienceCognitionMedicinePsychologyInternal medicineComputer science

Abstract

fetched live from OpenAlex

Abstract Mutations in the chromatin-remodelling factor ATRX underlie syndromic ID and ASD, yet the contribution of microglial ATRX to early brain development remains unknown. We used a tamoxifen-inducible Cx3cr1-CreERT2 system to delete Atrx in microglia during the first postnatal week, achieving >90% recombination at one month of age. At both one and three months, ATRX-null microglia displayed a sustained increase in CD68-positive phagocytic foci and in Ki67+ proliferative microglia, but an unexpected ∼20% reduction in microglial density, despite only modest evidence of caspase-3-mediated apoptosis. A comprehensive behavioural battery conducted between three and six months revealed normal anxiety, locomotion, learning, memory, social interaction and sensory gating, coinciding with a decline in knockout efficiency to ∼45% in cortex and ∼75% in hippocampus, suggestive of microglial repopulation by ATRX-expressing cells. These findings demonstrate that perinatal loss of ATRX drives chronic microglial reactivity and turnover with no discernable effects on neurobehaviours, suggesting a developmental resilience of neural circuits to transient microglial dysregulation.

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 score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
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 head0.020
GPT teacher head0.233
Teacher spread0.212 · 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

Citations0
Published2025
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicNeuroinflammation and Neurodegeneration Mechanisms→French-language works237,207→