A291 INHIBITORY EFFECTS OF GHRELIN ON MEMBRANE EXCITABILITY AND RESPONSES TO SATIETY MEDIATORS IN VAGAL AFFERENT NEURONS: INVOLVEMENT OF SUPPRESSOR OF CYTOKINE SIGNALING 3
Bibliographic record
Abstract
The orexigenic hormone ghrelin regulates feeding behavior via vagal afferent pathways. The mechanisms by which ghrelin exerts its inhibitory effects on nodose ganglion neurons are largely unknown. There is a evidence that ghrelin caused a significant increase in suppressor of cytokine signaling 3 (SOCS3) expression in nodose ganglion neurons, the cell bodies of vagal afferents. The aim of this study was to examine the effects of ghrelin on excitability and satiety mediator responses and whether SOCS3 is associated with the effects of ghrelin on nodose neurons. Nodose neurons from C57Bl6J mice were dissociated and incubated overnight with ghrelin (100 nM) and with/without zoledronic acid (ZA, a SOCS3 inhibitor, 10 mM). Current clamp recordings (to examine excitability) and Fura-2AM Ca2+-imaging (to examine responses to satiety mediators) were performed 18–24 h post-dissociation. Ghrelin (100 nM) significantly decreased the membrane potential (-52.0 ± 0.9 mV (n=18, control) vs. -61.5 ± 1.9 mV (n=15, ghrelin), unpaired student t-test, p<0.001) and increased the rheobase in nodose neurons (56.7 ± 5.4 pA (n=18, control) vs. 92.7 ± 8.6 pA (n=15, ghrelin), p<0.001). The number of action potential at twice rheobase correspondingly decreased by ghrelin (2.6 ± 0.4 (n=18, control) vs. 1.1 ± 0.1 (n=15, ghrelin), p<0.01). This reduction in membrane excitability was prevented in nodose neurons incubated with ZA (10 mM). The rheobase was reduced in ghrelin plus ZA-incubated neurons (ghrelin vs. ghrelin+ZA, 74.4 ± 4.4 pA, n=16, unpaired student t-test, p=0.064). The number of action potentials at twice rheobase was increased in ghrelin and ZA-incubated neurons (ghrelin vs. ghrelin+ZA, 1.8 ± 0.2, n=16, unpaired student t-test, p<0.05). The proportion of Ca2+ responses to CCK (100 nM) and 5-HT (1 mM) were examined in control and ghrelin-incubated nodose neurons. Proportion of neurons responding to CCK and 5-HT were significantly reduced by ghrelin. (CCK; control, 33/86, 38.4% vs. ghrelin-incubated, 9/49, 18.4%, Fisher’s exact test, p<0.05, 5-HT; control, 22/63, 34.9% vs. ghrelin-incubated, 10/59, 14.5%, p<0.05). Ghrelin reduced the membrane excitability and satiety responses in nodose ganglion neurons and this inhibitory effect was reversed by the inhibition of SOCS3. Thus, ghrein-SOCS3 pathway might be responsible for the inhibitory mechanism in vagal afferents and a potential therapeutic target in obesity. CIHR
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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) | 0.002 | 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".