Locally Synthesized Calcitonin Gene-Related Peptide Has a Critical Role in Peripheral Nerve Regeneration
Bibliographic record
Abstract
Regeneration of peripheral nerves involves complex and intimate interactions between axons and Schwann cells. Here, we show that local axon synthesis and action of the neuropeptide calcitonin gene-related peptide (CGRP) is critical for this collaboration. After peripheral sural sensory axon injury in rats, we observed an unexpectedly large proportion of axons that newly expressed CGRP during regeneration. Intense peptide expression accompanied local rises in alphaCGRP mRNA in the nerve trunk, and there was evidence of transport of alphaCGRP mRNA into regenerating axons, indicating intra-axonal peptide synthesis. Calcitonin gene-related peptide receptor and its receptor activity modifying protein were expressed onadjacent Schwann cells, where they were available for signaling. Moreover, exogenous CGRP induced proliferation in isolated adult Schwann cells. New axon outgrowth and CGRP expression depended on local peptide synthesis and were inhibited by exposure tolocal translation inhibitors. Local delivery of siRNAs to either alphaCGRP or receptor activity modifying protein 1 to sites of nerve transection was associated with severe disruption of axon outgrowth.These findings indicate that robust localized intra-axonal translation of the CGRP neuropeptide during regeneration signals Schwann cell proliferation, behavior that is critical for partnering during adult peripheral nerve regrowth.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".