Oxidatively damaged DNA in DNA repair-deficient and ethanol-exposed fetal brains induces gene dysregulation and mitochondrial dysfunction associated with neurodevelopmental disorders
Bibliographic record
Abstract
Oxidatively damaged DNA caused by reactive oxygen species (ROS) in the fetal brain contributes to neurodevelopmental disorders (NDDs), but the mechanism is unclear. We investigated the impact of this DNA damage on the developing fetal brain using a DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mouse model, exposed during pregnancy to physiological (saline)- and ethanol (EtOH)-enhanced ROS levels. Oxidatively damaged DNA in saline-exposed Ogg1 KO vs. wild-type (WT) fetal brains was increased, and further enhanced by EtOH exposure. These OGG1-and EtOH-dependent patterns of DNA damage were reflected in: (a) increased gene dysregulation in saline-exposed KO brains, and greatly exacerbated by EtOH, notably in the long-term synaptic potentiation pathway, crucial for learning and memory; (b) impaired mitochondrial metabolism in cultured primary Ogg1 KO neurons; and, (c) sex-dependent learning and memory disorders. These results suggest oxidatively damaged DNA in DNA repair-deficient fetal brains contributes to NDDs by altering gene expression and mitochondrial metabolism.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 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 teacher head, 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".