Bibliographic record
Abstract
Treatment of Long Evans hooded rats during development with the cholesterol synthesis inhibitor AY9944 (AY) produces atypical absence seizures with slow spike-and-wave discharges (SSWDs). The purpose of this study was to determine the role of both male and female sex hormones on atypical absence seizures in the AY model. Initially, a time course study was performed that examined the effects of the female estrous cycle on the chronic SSWDs, γ-aminobutyric B receptor (GABA BR) binding, and GABA BR protein expression. It was found that there was a significant increase in both the duration of SSWD and GABA BR binding in the AY model during the proestrus stage of the estrous cycle, the stage during which the levels of progesterone are at their highest. No changes in GABA BR1a or R2 protein levels were observed across the cycle. Subsequently, a pharmacological study using progesterone, allopregnanolone (progesterone metabolite), 17 β-estradiol and testosterone was performed to determine their effects on AY-induced seizures. It was found that the administration of both progesterone and allopregnanolone exacerbated seizures in the AY model, whereas 17 β-estradiol and testosterone attenuated the SSWD duration. Interestingly, protein analysis revealed that GABA BR2 levels in the cortex and hippocampus decreased in a time dependent manner after testosterone was administered in AY-treated animals. Finally, we examined the effects of hormone receptor blockers and inhibitors of metabolism. Mifepristone (intracellular progesterone receptor antagonist), tamoxifen (intracellular estrogen receptor antagonist), flutamide (intracellular testosterone receptor antagonist) and finasteride (a metabolite inhibitor of both progesterone and testosterone) were used. Our results showed that neither mifepristone, tamoxifen nor flutamide blocked the effects of progesterone, 17 β-estradiol or testosterone, respectively, on SSWD duration in the AY model, suggesting that these three sex hormones are working in a manner independent of their intracellular receptors. Our experiments with finasteride indicated that both progesterone and testosterone are working via their metabolites in the AY model. These data suggest an important role for steroid hormones in the regulation and maintenance of AY-induced atypical absence seizures. In addition, further studies on the GABAergic mechanism of action of testosterone may be very useful for the development of new anti-absence medications. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
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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) | 0.000 | 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) | 0.001 | 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 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".