Sex-specific transcriptional signatures in the medial prefrontal cortex underlying sexually dimorphic behavioural responses to stress in rats
Bibliographic record
Abstract
Background: Converging evidence suggests that stress alters behavioural responses in a sex-specific manner; however, the underlying molecular mechanisms of stress remain largely unknown. Methods: We adapted unpredictable maternal separation (UMS) and adult restraint stress (RS) paradigms to mimic stress in rats in early life or adulthood, respectively. The sexual dimorphism of the prefrontal cortex was noted, and we performed RNA sequencing (RNA-Seq) to identify specific genes or pathways responsible for sexually dimorphic responses to stress. We then performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the results of RNA-Seq. Results: Female rats exposed to either UMS or RS showed no negative effects on anxiety-like behaviours, whereas the emotional functions of the PFC were impaired markedly in stressed male rats. Leveraging differentially expressed genes (DEG) analyses, we identified sex-specific transcriptional profiles associated with stress. There were many overlapping DEGs between UMS and RS transcriptional data sets, where 1406 DEGs were associated with both biological sex and stress, while only 117 DEGs were related to stress. Notably, Uba52 and Rpl34-ps1 were the first-ranked hub gene in 1406 and 117 DEGs respectively, and Uba52 was higher than Rp134-ps1, suggesting that stress may have led to a more pronounced effect on the set of 1406 DEGs. Pathway analysis revealed that 1406 DEGs were primarily enriched in ribosomal pathway. These results were confirmed by qRT-PCR. Limitations: Sex-specific transcriptional profiles associated with stress were identified in this study, but more in-depth experiments, such as single-cell sequencing and manipulation of male and female gene networks in vivo, are needed to verify our findings. Conclusion: Our findings show sex-specific behavioural responses to stress and highlight sexual dimorphism at the transcriptional level, shedding light on developing sex-specific therapeutic strategies for stress-related psychiatric 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) | 0.000 | 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".