Interleukin-17A (IL-17A) enhances axonal regeneration and mitochondrial function of normal and diabetic sensory neurons
Bibliographic record
Abstract
Rationale and hypothesis: Diabetic neuropathy involves dying back of nerve endings that reflects impairment in axonal plasticity and regenerative nerve growth. Metabolic changes in diabetes can lead to a dysregulation of hormonal mediators, such as cytokines. Thus I studied the effect of interleukin-17A (IL-17A), a proinflammatory cytokine produced by T-cells, on the phenotype of sensory neurons derived from control or diabetic rats. I hypothesized that IL-17A induces neurite outgrowth in sensory neurons through signaling pathways that enhance mitochondrial function. IL-17A can also reverse impaired nerve regeneration associated with diabetes Objectives: Determine the ability of IL-17A to enhance neurite outgrowth in cultured sensory neurons. Investigate the signalling pathways activated by IL-17A and mechanistically link to neurite outgrowth. Study the ability of IL-17A to improve mitochondrial function of sensory neurons (since axon outgrowth consumes high levels of ATP). Methodology: Cultured adult dorsal root ganglia (DRG) sensory neurons derived from age matched control or streptozotocin (STZ)-induced type 1 diabetic rats were fixed and stained for fluorescent imaging to determine total neurite outgrowth. Western blotting determined the levels of MAPK and PI-3K activation by IL-17A and for measuring levels of proteins of mitochondrial oxidative phosphorylation pathway. Mitochondrial bioenergetic function was tested in cultured DRG neurons using the Seahorse XF Analyzer. Results: I found that IL-17A (10 ng/ml; P<0.05) significantly increased total neurite outgrowth in cultures derived from both control and STZ-diabetic rat models. This enhancement was mediated by IL-17A-dependent activation of MAPK and PI-3K pathways with maximal effect at 15 minutes (P<0.05). Pharmacological blockade of one of these activated pathways led to total inhibition of neurite outgrowth. IL-17A improved mitochondrial bioenergetic function of sensory neurons. Bioenergetics function was associated with augmented expression of proteins of mitochondrial oxidative phosphorylation. Conclusion: IL-17A enhanced axonal plasticity through activation of MAPK and PI-3K pathways and was associated with augmented mitochondrial bioenergetics function in sensory neurons
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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".