PS116. Desvenlafaxine prevents white matter injury and improves the decreased phosphorylation of rate-limiting enzyme of cholesterol synthesis in a chronic mouse model of depression.
Bibliographic record
Abstract
Abstract Objective: Serotonin/norepinephrine reuptake inhibitors antidepressants exert their effects by increasing serotonin and norepinephrine in the synaptic cleft. Studies show it takes 2–3 weeks for the mood-enhancing effects, which indicates other mechanisms may underlie their treatment effects. Here, we investigated the role of white matter in treatment and pathogenesis of depression using an unpredictable chronic mild stress (UCMS) mouse model. Methods: Desvenlafaxine (DVS) was orally administrated to UCMS mice at the dose of 10mg/kg/day one week before they went through 7 weeks stress procedure and lasted for over 8 weeks before the mice being sacrificed. Results: No significant changes were found for protein markers of neurons and astrocytes in UCMS mice. However, myelin and oligodendrocyte related proteins were significantly reduced in UCMS mice. DVS prevented the stress-induced injury to white matter and the decrease of phosphorylated 5'-AMP-activated protein kinase (AMPK-α) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) protein expression. DVS increased open arm entries in elevated plus maze, sucrose consumption in sucrose preference test and decreased immobility in tail suspension and forced swimming tests. Summary: These findings suggest stress induces depression-like behaviors and white matter deficits in UCMS mice. DVS may ameliorate the oligodendrocyte dysfunction by affecting cholesterol synthesis, alleviating the depression-like phenotypes in these mice.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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".