Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2 <sup>−</sup> knockin mice
Bibliographic record
Abstract
Abstract Prostaglandin E2 (PGE2) is a bioactive signalling molecule metabolized from the phospholipid membranes by the enzymatic activity of cycloxygenase‐2 (COX‐2). In the developing brain, COX‐2 constitutively regulates the production of PGE2, which is important in neuronal development. However, abnormal COX‐2/PGE2 signalling has been linked to neurodevelopmental disorders including autism spectrum disorders (ASDs). We have previously demonstrated that COX‐2 − ‐KI mice show autism‐related behaviours including social deficits, repetitive behaviours and anxious behaviours. COX‐2‐deficient mice also have deficits in pathways involved in synaptic transmission and dendritic spine formation. In this study, we use a Golgi–COX staining method to examine sex‐dependent differences in dendritic and dendritic spine morphology in neurons of COX‐2 − ‐KI mice cerebellum compared with wild‐type (WT) matched controls at postnatal day 25 (P25). We show that COX‐2 − ‐KI mice have increased dendritic arborization closer to the cell soma and increased dendritic looping. We also observed a sex‐dependent effect of the COX‐2 − ‐KI on dendritic thickness, dendritic spine density, dendritic spine morphology, and the expression of β‐actin and the actin‐binding protein spinophilin. Our findings show that changes in COX‐2/PGE2 signalling lead to impaired morphology of dendrites and dendritic spines in a sex‐dependant manner and may contribute the pathology of the cerebellum seen in individuals with ASD. This study provides further evidence that the COX‐2 − ‐KI mouse model can be used to study a subset of ASD pathologies.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".