Tumor Necrosis Factor Alpha Increases Excitability in Subfornical Organ Neurons
Bibliographic record
Abstract
Tumor necrosis factor‐alpha (TNFα) is a pro‐inflammatory cytokine implicated in cardiovascular diseases involving hypertension. It has been shown that TNFα −/− mice do not develop angiotensin II‐induced hypertension, although the mechanism for this is unknown. Recent studies suggest that the subfornical organ (SFO) is critical for TNFα's hypertensive effects. We therefore used patch clamp techniques to examine both acute and longer term effects of TNFα's on the excitability of dissociated SFO neurons. It was found that bath application of 500 pM TNFα induced acute depolarizations in 58% (n = 11/19) of SFO neurons tested (mean depolarization of 6.7 ± 0.8 mV, n = 11). TNFα's acute effects were concentration‐dependent with depolarizing effects observed on SFO neurons at 50 pM (44%, mean depolarization of 6.8 ± 1.0 mV, n = 7/16), and 500fM (22%, mean depolarization of 3.1 ± 0.4 mV, n = 2/9). SFO neurons incubated with TNFα for 24 hours at 575 pM showed increased action potential frequency compared to control SFO neurons (3.7 ± 1.3 Hz, TNFα, n = 7, 0.4 ± 0.2 Hz, control, n = 7, p < 0.05, Student's t‐test). Additionally, TNFα incubation reduced the action potential threshold relative to control (rheobase = 5.5 ± 0.7 pA, TNFα, n = 6, rheobase = 12 ± 1.8 pA, control, n = 6, p < 0.01, Student's t‐test). Furthermore, TNFα incubation was found to increase the magnitude of transient Na + currents (I Na ) compared to control (2.7 ± 0.2 nA, TNFα, n = 12, 1.7 ± 0.1 nA, control, n = 15, p < 0.001, Student's t‐test). Lastly, it was observed that TNFα incubation shifted the activation of voltage‐gated Na + channels to a more hyperpolarized state (V 1/2 = −34.5 ± 0.8 mV, TNFα, n = 12, V 1/2 = −30.2 ± 1.2 mV, control, n = 11, p < 0.001, Student's t‐test). These data suggest that TNFα is increasing the acute and long‐term excitability in SFO neurons, and this long‐term effect is influenced by I Na modulation. Support or Funding Information 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) | 0.001 | 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".