The 43rd Annual Meeting of the Canadian College of Neuropsychopharmacology, November 4, 2021
Bibliographic record
Abstract
Background: Depression is a prevalent psychiatric disorder characterized by heterogeneous symptoms that can last a lifetime and remain even after several courses of antidepressant treatments.Vulnerability to depression is associated with long-lasting changes in the transcriptional profile of the nucleus accumbens (NAcc), a brain region involved in reward and mood regulation.Methods: Here, we characterized the enduring changes in histone modifications in the NAcc of mice exposed to chronic social defeat stress (CSDS), a validated model for the study of depression-like behaviours that separates mouse populations into susceptible (SUS) and resilient (RES) based on a social interaction test (SIT).Tissue from the NAcc of control, SUS, and RES mice was collected either 24 hours or 4 weeks after the SIT and processed for histone profiling via mass spectrometry.In parallel, we mapped the genome-wide enrichment of the most changed histone modifications using CUT&RUN and assessed for chromatin accessibility in a cell-specific manner using ATAC-Seq.Results: CSDS alters the methylation (me) dynamics of lysine (K) 27 of the histone variant H3.3 -the predominant form of H3 present in adult brain neurons.Specifically, we observed an increase in the abundance of H3.3K27me1 and a decrease in the abundance of H3.3K27me2 in the NAcc of SUS mice.Gen omic distribution shows that H3.3K27me1 is primarily enriched in gene bodies and proximal promoters, suggesting its crucial role in determining stress-induced transcriptional profiles.In contrast, H3.3K27me2 is weakly deposited across intergenic regions.Using bioinformatics, we are currently identifying changes of chromatin accessibility and functional regulatory elements that coincide with H3.3K27me1 enrichment.Conclusion: Our results suggest that H3.3K27me1 and H3.3K27me2 are important chromatin "scars" that mediate enduring susceptibility to stress in the NAcc.Understanding the molecular basis of these adaptations and identifying the genomic regions affected will shed new light on persisting forms of stress-induced pathology.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.334 | 0.145 |
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".