Hippocampal reelin and GAD67 gene expression and methylation in the GFAP.HMOX1 mouse model of schizophrenia
Bibliographic record
Abstract
Schizophrenia is a complex neuropsychiatric disorder featuring enhanced brain oxidative stress and deficient reelin protein. GFAP .HMOX1 0-12m mice that overexpress heme oxygenase-1 (HO-1) in astrocytes manifest a schizophrenia-like neurochemical, neuropathological and behavioral phenotype including brain oxidative stress and reelin downregulation . We used RT-PCR, targeted bisulfite next-generation sequencing, immunohistochemistry and in situ hybridization on hippocampal tissue of GFAP .HMOX1 0-12m mice to delineate a possible molecular mechanism for the downregulation of reelin and to identify the neuronal and non-neuronal (glial) cell types expressing reelin in our model. We found reduced reelin and increased DNMT1 and TET1 mRNA expression in the hippocampus of male GFAP .HMOX1 0-12m mice and reduced GAD67 mRNA expression in females. These mRNA changes were accompanied by sexually dimorphic alterations in DNA methylation levels of Reln and Gad1 genes. Reelin protein was expressed by oligodendrocytes and GABAergic interneurons , but not by astrocytes or microglia in GFAP.HMOX1 0-12m and wild-type brains of both sexes. Reelin mRNA was also observed in oligodendrocytes . Moreover, a significant downregulation of reelin-expressing oligodendrocytes was detected in the hippocampal dentate gyrus of male GFAP.HMOX1 0-12m mice. These results suggest a novel mechanism for brain reelin depletion in schizophrenia. Containment of the astrocytic HO-1 cascade by pharmacological or other means may protect against stress-induced brain reelin depletion in schizophrenia and other neurodevelopmental disorders.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".