Impaired macroglial development and axonal conductivity contributes to the neuropathology of DYRK1A-related intellectual disability syndrome
Bibliographic record
Abstract
Abstract The correct development and activity of neurons and glial cells is necessary to establish proper brain connectivity. DYRK1A encodes a protein kinase involved in the neuropathology associated with Down syndrome that influences neurogenesis and the morphological differentiation of neurons. DYRK1A loss-of-function mutations in heterozygosity cause a well-recognizable syndrome of intellectual disability and autism spectrum disorder. In this study, we analysed the developmental trajectories of macroglial cells and the properties of the corpus callosum, the major white matter tract of the brain, in Dyrk1a+/− mice, a mouse model that recapitulates the main neurological features of DYRK1A syndrome. We found that Dyrk1a+/− haploinsufficient mutants present an increase in astrogliogenesis in the neocortex and a delay in the production of cortical oligodendrocyte progenitor cells and their progression along the oligodendroglial lineage. There were fewer myelinated axons in the corpus callosum of Dyrk1a+/− mice, axons that are thinner and with abnormal nodes of Ranvier. Moreover, action potential propagation along myelinated and unmyelinated callosal axons was slower in Dyrk1a+/− mutants. All these alterations are likely to affect neuronal circuit development and alter network synchronicity, influencing higher brain functions. These alterations highlight the relevance of glial cell abnormalities in neurodevelopmental disorders.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".