Oligodendrogenesis Inhibition in the Juvenile and Adolescent Periods Differentially Alters Myelin in Mice
Bibliographic record
Abstract
INTRODUCTION: The timing of myelination during development varies spatially according to the evolving functional demands of the maturing brain and is likely a mechanism of plasticity that contributes to sensitive periods of brain development during which the brain has heightened susceptibility to environmental influences. Disruption to this myelination process is therefore likely to have spatially and temporally heterogeneous effects. Myelinating oligodendrocytes arise from the differentiation of oligodendrocyte precursor cells, a process that depends on the transcription factor Myrf. In this study, the inducible Myrf conditional knockout mouse model is leveraged to characterize the impact of inhibiting oligodendrogenesis during the juvenile or adolescent period on white matter tracts with different timing of maturation. METHODS: Electron microscopy (EM) was used to quantify the fraction of myelinated axons, axon diameter, and myelin thickness, or T2- and diffusion-weighted MRI (dMRI) were used to compute white matter volumes and measures sensitive to microstructure. RESULTS: Mice with inhibited oligodendrogenesis during the juvenile period had a lower fraction of myelinated axons in the corpus callosum, which was not the case when oligodendrogenesis was halted during adolescence. Halting oligodendrogenesis in either developmental period had no effect on myelinated fraction in the earlier-to-mature optic tracts. Halted oligodendrogenesis during the juvenile period was detected with MRI as decreased volume of late-myelinating structures (corpus callosum, anterior commissure, and fornix) relative to controls. No group differences were observed in dMRI measures. Additionally, thinner myelin on larger calibre axons in the optics tracts of adolescent mice with halted oligodendrogenesis was detected with EM, but no MRI measures were sensitive to this difference. CONCLUSION: This study demonstrates that the impact of disrupting developmental oligodendrogenesis on white matter differs depending on the timing of disruption relative to the developmental stage of the structure. The results also highlight that morphological measures from structural MRI have high sensitivity to disrupted developmental myelination of white matter tracts.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
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".