Prostaglandin E<sub>2</sub> Mediates Cellular Effects of Interleukin‐1β on Parvocellular Neurones in the Paraventricular Nucleus of the Hypothalamus
Bibliographic record
Abstract
Abstract Interleukin-1beta (IL-1beta) is involved in hypothalamic regulation of corticotrophin-releasing hormone secretion, autonomic activation and consequent downstream modulation of the neuroimmune response. Previously, we have shown that IL-1beta depolarises parvocellular neurones in the paraventricular nucleus (PVN) of the hypothalamus, and these effects are dependent on attenuation of gamma-amino butyric acid (GABA)-ergic input. In the present study, using whole-cell patch clamp recordings of rat neurones in a slice preparation of the PVN, we show that the effects of IL-1beta are abolished in the presence of a cyclooxygenase (COX)-2 inhibitor, NS-398, indicating a dependence on prostaglandin (PG) synthesis and activation. In response to 1 microM PGE2, 64% of parvocellular neurones tested exhibited a clear depolarisation, which was abolished in the presence of tetrodotoxin (TTX). Furthermore, neurones responsive to both IL-1beta and PGE2 exhibited a decrease in the frequency of inhibitory post-synaptic potentials, suggesting that effects of these modulators are mediated via a decrease in GABA-ergic input to these neurones. A proportion (44% and 40%, respectively) of putative GABA-ergic neurones in the halo region surrounding the PVN demonstrated hyperpolarising responses to 1 nM IL-1beta and 1 microM PGE2, and these effects were maintained in TTX. Furthermore, direct hyperpolarising effects of IL-1beta were blocked in the presence of NS-398. Together, these data suggest that PGE2, synthesised in response to IL-1beta-activation of COX-2 expressing cells, directly hyperpolarises putative GABA-ergic neurones in the halo zone surrounding and projecting to the PVN, resulting in a decrease in GABA-ergic input to parvocellular neurones and consequent depolarisation. These data further elucidate the cellular mechanisms by which IL-1beta exerts its neuroimmune-related actions in the PVN.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".