Tumor necrosis factor alpha influences the excitability of subfornical organ neurons and potentiates angiotensin II-induced calcium activity
Bibliographic record
Abstract
Cardiovascular disease is a leading cause of mortality worldwide. Progress has been made in diagnosing and treating this condition, however the mechanisms by which it develops have yet to be fully elucidated. Accumulating evidence suggests that inflammation plays an important role in cardiovascular disease. Cytokines are elevated in patients with hypertension and heart failure, as well as in animal models of these conditions. Tumor necrosis factor alpha (TNFα), a cytokine, has been shown to increase blood pressure and sympathetic output, and it is critical in the development of hypertension. It has been determined that the subfornical organ (SFO) of the central nervous system mediates the effects of TNFα. Knockdown of the TNFα receptor in the SFO ameliorates sympathoexcitation following heart failure, further suggesting a mechanism by which TNFα acts in the SFO to regulate cardiovascular function. However, it is unknown how TNFα modulates SFO neurons to cause these effects. Therefore, we performed whole-cell patch-clamp electrophysiology and [Ca2+]i imaging on dissociated SFO neurons isolated from male Sprague-Dawley rats to determine their activity in response to TNFα. We found that acute application of TNFα depolarized 50% of SFO neurons and increased their firing rate. We also found that chronic treatment of SFO neurons with TNFα increased their excitability, an effect that was mediated, at least in part, by a hyperpolarizing shift in the activation threshold of the voltage-gated Na+ current. Furthermore, we observed that TNFα potentiated angiotensin II-induced increases in [Ca2+]i in SFO neurons. This effect was also mediated by the voltage-gated Na+ current, as tetrodotoxin prevented this potentiation. These data suggest cellular mechanisms by which TNFα increases blood pressure and sympathetic activity through actions in the SFO, and thus provide new insight into how circulating inflammatory cytokines may contribute to cardiovascular regulation in health and disease.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 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".