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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Cell Death and Survival

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1536347

This article is part of the Research Topic 7th International Symposium on Peripheral Nerve Regeneration: Peripheral Nerve Regeneration - Advances and New Directions View all 8 articles

DA.Vra1-congenic rats display increased gene expression and Schwann cell apoptosis, but unaffected nerve regeneration compared to parental DA rats after sciatic nerve injury and repair

Provisionally accepted
  • 1 Department of Translational Medicine - Hand surgery, Lund University, Lund, Sweden
  • 2 Department of Experimental Medicine, Lund University, Lund, Skane County, Sweden

The final, formatted version of the article will be published soon.

    The rat Vra1 locus, containing Glutathione S-transferase alpha 4 (Gsta4), regulates degeneration of CNS neurons in toxin-, protein-and injury-based models. We hypothesize that PVG alleles in Vra1 confer protection and increased axonal outgrowth after peripheral nerve injury and repair. DA rats (n=14) and DA rats with PVG alleles in Vra1 locus (DA.Vra1, n=14) were subjected to sciatic nerve transection and immediate repair. After six days, axonal outgrowth, protein-and gene expression were analyzed in injured and uninjured nerves and in dorsal root ganglia (DRG). No differences in axonal outgrowth were observed between strains, but apoptotic Schwann cell number in injured distal nerve end was higher in DA.Vra1 compared to DA rats (p=0.003). In both strains, gene-and protein expression of activating transcription factor 3 (ATF3) and 27-kDa heat shock protein (HSP27, i.e. Hspb1) was increased in injured vs. uninjured DRG. In DA.Vra1 rats, Gsta4 gene expression was lower in injured vs. uninjured DRG (p=0.043), but higher compared to DA in injured nerve (p=0.008) and injured DRG (p=0.008). DA.Vra1 had higher gene expression of Atf3 (p=0.016) and caspase 3 (p=0.032) in injured nerves compared to DA rats. Results highlight

    Keywords: nerve injury1, nerve regeneration2, ATF33, cleaved caspase 34, c-Jun5, Apoptosis6, Hspb17, Vra18

    Received: 28 Nov 2024; Accepted: 10 Mar 2025.

    Copyright: © 2025 Stenberg, Jewett, Dueñas Rey, Swanberg and Dahlin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lars B Dahlin, Department of Translational Medicine - Hand surgery, Lund University, Lund, Sweden

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