Prophylactic Valproic Acid Treatment Prevents Schizophrenia-Related Behaviour in Disc1-L100P Mutant Mice
Bibliographic record
Abstract
BACKGROUND: Schizophrenia is a neurodevelopmental disorder with onset early in adulthood. Disrupted-In-Schizophrenia-1 (DISC1) is a susceptibility gene for schizophrenia and other psychiatric disorders. Disc1-L100P mutant mice show behaviors relevant to schizophrenia at 12 weeks, but not at 8 weeks of age, and may be useful for investigating the onset of schizophrenia in early adulthood. METHODS: We investigated whether early valproic acid treatment would prevent behavioral, cellular and gene expression abnormalities in Disc1-L100P mutants. RESULTS: Valproic acid prevented hyperactivity and deficits in prepulse inhibition and latent inhibition in Disc1-L100P mice. Genome-wide transcription profiling identified Lcn2 (lipocalin2) transcripts as being elevated by the Disc1 mutation and corrected by valproate. Disc1-L100P mice also had increased glial cell numbers in the subventricular zone, which was normalized by valproate. Genetic deletion of Lcn2 normalized glial cell numbers and behavior in Disc1-L100P mutants. CONCLUSIONS: Pharmacological treatments are a feasible way of preventing abnormal behaviour in a genetic model of schizophrenia. Lcn2 is a potential novel drug target for early intervention in schizophrenia.
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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".