Dissecting the role of prostaglandin E₂ EP2 receptor signaling in MCH neurons in sex-dependent modulation of anxiety, memory and hippocampal synaptic transmission under western diet
Bibliographic record
Abstract
Melanin-concentrating hormone (MCH) neurons are known to regulate energy balance, food intake, anxiety, memory, and cognition. Prostaglandin E₂ (PGE2) can depolarize these neurons via EP2 receptors under western diet (WD) conditions, which contributes to diet-induced obesity. To determine how WD-induced activation of MCH neurons affects other function of these cells, this research examined the sex- and diet-specific effects of EP2 receptor (EP2R) deletion in MCH neurons on anxiety-like behaviors, memory performance, and synaptic plasticity. Male and female mice with MCH neuron-specific EP2R knockout (KO) were assessed under chronic standard chow or WD conditions using behavioral assays and electrophysiological recordings. EP2R KO significantly reduced anxiety-like behaviors in male mice on a WD, evidenced by decreased thigmotaxis in the open field test, while differences in thigmotaxis were absent in all females and chow-fed males. In the novel object recognition test, male EP2R KO mice exhibited increased novel object preference under standard chow conditions compared to WD KO mice, while EP2R KO protected females from WD-induced memory impairments. Finally, electrophysiological experiments in transverse dorsal hippocampal brain slices revealed higher neurotransmitter release probability in female EP2R KO chow-fed mice, as well as an enhanced post-tetanic potentiation in chow-fed male EP2R KO mice compared to chow controls, while no changes were seen in long-term potentiation. These findings highlight the complex interplay between diet, sex, and EP2R signaling in MCH neurons. Thus, EP2Rs in MCH neurons may play a role in high-fat diet-induced changes in mood and cognitive function.
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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 | 0.001 |
| 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".