Hyperactive mice show elevated D2High receptors, a model for schizophrenia: calcium/calmodulin‐dependent kinase II alpha knockouts
Bibliographic record
Abstract
The cerebral frontal cortex of schizophrenia patients shows elevated levels of RNA for calcium/calmodulin‐dependent protein kinase II beta (CaMKIIβ). In addition, recent research shows that animal models for schizophrenia consistently show elevated levels of dopamine 2 receptors in their high‐affinity state (D2High), the major target for antipsychotic medication. The present study was done to examine whether an alteration in the levels of CaMKIIβ, in respect to CaMKIIα, could lead to altered levels of D2High receptors. We used quantitative real‐time PCR to measure CaMKIIα and CaMKIIβ mRNA levels in heterozygous and wild type CaMKIIα knock‐out mice, which show reduced CaMKIIα levels, and a D2R binding assay to determine the levels of D2High. The heterozygous CaMKIIα knock‐out mice, which show features analogous to schizophrenia, showed a 50% reduction in CaMKIIα mRNA, and no change in CaMKIIβ in the frontal cortex, as expected, but also a 29% upregulation of CaMKIIβ mRNA in the striatum and a 2.8‐fold increase in D2High receptors. In addition, we found that the CaMKII inhibitor, KN‐93, markedly reduced D2High states in rat striatum. The elevated levels of CaMKIIβ mRNA in the striatum suggest that this enzyme may increase D2High in animals and possibly in schizophrenia itself.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".