Mechanism of glucocorticoid-induced oxidative stress in rat hippocampal slice cultures
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Bibliographic record
Abstract
Prolonged stress results in elevation of glucocorticoid (GC) hormones, which can have deleterious effects in the brain. The hippocampus, which has a high concentration of glucocorticoid receptors, is especially vulnerable to increasing levels of GCs. GCs have been suggested to endanger hippocampal neurons by exacerbating the excitotoxic glutamate-calcium-reactive oxygen species (ROS) cascade. In an effort to reveal the mechanisms underlying GC-mediated hippocampal neurotoxicity, we aimed to clarify the molecular pathway of GC-induced ROS increase by using organotypic hippocampal slice cultures. Assays for ROS, using 2',7'-dichlorodihydrofluorescein diacetate fluorescence, showed that treatment of synthetic GC, dexamethasone (DEX) significantly enhanced ROS levels. Time course and dose response analyses indicated that peak amount of ROS was generated at 4 h after treatment with 50 micromol/L DEX. By contrast, other steroid hormones, progesterone and estradiol did not influence ROS production. N-acetyl-L-cysteine completely suppressed ROS produced by DEX. Propidium iodide staining exhibited prominent cell death in the hippocampal layer after 96 h of DEX treatment. RU486, a GC receptor antagonist, almost completely blocked the effect of DEX on ROS production and cell death, indicating that DEX-induced ROS overproduction and hippocampal death are mediated via GC receptors. Real-time reverse transcriptase PCR analysis demonstrated that after DEX treatment the level of glutathione peroxidase mRNA was decreased whereas that of NADPH oxidase mRNA was significantly enhanced. These findings suggest that excess GCs cause hippocampal damage by regulating genes involved in ROS generation.
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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 it