Sox2 Ablation in the Suprachiasmatic Nucleus Perturbs Anxiety- and Depressive-like Behaviors
Bibliographic record
Abstract
Mood disorders negatively impact the lives of hundreds of millions of individuals worldwide every year, yet the precise molecular mechanisms by which they manifest remain elusive. Circadian dysregulation is one avenue by which mood disorders are thought to arise. SOX2 is a transcription factor that is highly expressed in the murine suprachiasmatic nucleus (SCN), the circadian master clock, and has been recently found to be an important regulator of Per2, a core component of the molecular clock. Genetic ablation of the Sox2 gene in GABAergic neurons selectively impacts SCN neurons, as they are one of very few, if not the only, GABAergic populations that express Sox2. Here, we show that GABAergic-restricted ablation of Sox2 results in anxio-depressive-like phenotypes in mice as observed in the elevated plus maze, forced swim test, tail suspension test, and sucrose preference test. We further observe a reduction in basal and/or forced swim-induced c-Fos expression, a marker of neuronal activation, in the nucleus incertus, arcuate nucleus, and dentate gyrus of Sox2 conditional knockout (cKO) mice. Given the restricted disruption of SOX2 expression in the SCN of Sox2 cKO mice, we propose that their mood-associated phenotypes are the consequence of a dysregulated central clock that is unable to communicate appropriately timed signals to other brain nuclei that regulate affective behaviors.
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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".