123-OR: Short-Term Hyperglycemia Causes a Paradoxical Reduction in Sensory Neuron Excitability
Bibliographic record
Abstract
Peripheral neuropathy in diabetes is characterized by a constellation of sensory abnormalities, including numbness, tingling, as well as exacerbated responses to painful and non-painful stimuli. Particular interest has concentrated on voltage-gated sodium (Nav) channels since they play central roles in painful forms of neuropathy in long-term diabetes. However, their possible contributions to the onset of neuropathy are still under investigation. In the current study, we aimed at elucidating the contribution of Nav channels during early hyperglycemia in sensory neurons from the Dorsal Root Ganglion (DRG). We used cultured DRG neurons, maintained in either control (5 mM glucose) or in high glucose media (25 mM) for up to 14 days, and intact DRG tissues from streptozotocin (STZ)-induced hyperglycemic mice (at 1 and 3 months after induction). To study Nav channel function we used whole-cell patch-clamp electrophysiology and biochemical analysis by Western blotting for the detection of Nav subunit expression. Our results indicate that DRG neurons maintained in high glucose showed reduced action potential firing frequency and reduced inward currents. The later was consistent with the downregulation of the tetrodotoxin sensitive (TTX-S) Nav1.3, Nav1.6, and Nav1.7 subunits in intact DRG tissues from one-month STZ-hyperglycemic mice. The Navβ2 subunit, which has been shown to regulate the cell surface expressions of TTX-S Nav channels, also shows reduced expression levels. Interestingly, after three months of STZ-induced hyperglycemia, there was a significant upregulation in the expression level of the TTX-S Nav1.7 subunit, which has been linked to painful forms of neuropathy. Taken together, our data revealed that changes in expression and function of TTX-S Nav subunits take place from the early stage of pathologic hyperglycemia. Therefore, our data suggest that Nav channel may be involved in the development of positive and negative sensory symptoms in diabetic neuropathy. Disclosure V.A. Campanucci: None. M. Bautista: None. J.T. Neapetung: None. Funding Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-03958)
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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) | 0.004 | 0.001 |
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".