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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

Stenberg, Lena LU orcid ; Jewett, Michael ; Dueñas Rey, Alfredo LU ; Swanberg, Maria LU and Dahlin, Lars B. LU orcid (2025) In Frontiers in Cell and Developmental Biology 13.
Abstract

Introduction: The rat Vra1 locus, containing glutathione S-transferase alpha 4 (Gsta4), regulates the degeneration of central nervous system (CNS) neurons in toxin-, protein-, and injury-based models. We hypothesize that Piebald Virol Glaxo.1AV1 (PVG) alleles in Vra1 confer protection and increased axonal outgrowth after peripheral nerve injury and repair. Methods: DA rats (n = 14) and DA rats with PVG alleles in the Vra1 locus (DA.Vra1, n = 14) were subjected to sciatic nerve transection and immediate repair. After 6 days, axonal outgrowth and protein and gene expression were analyzed in injured and uninjured nerves and dorsal root ganglia (DRG). Results: No differences in axonal outgrowth were observed between strains, but the number... (More)

Introduction: The rat Vra1 locus, containing glutathione S-transferase alpha 4 (Gsta4), regulates the degeneration of central nervous system (CNS) neurons in toxin-, protein-, and injury-based models. We hypothesize that Piebald Virol Glaxo.1AV1 (PVG) alleles in Vra1 confer protection and increased axonal outgrowth after peripheral nerve injury and repair. Methods: DA rats (n = 14) and DA rats with PVG alleles in the Vra1 locus (DA.Vra1, n = 14) were subjected to sciatic nerve transection and immediate repair. After 6 days, axonal outgrowth and protein and gene expression were analyzed in injured and uninjured nerves and dorsal root ganglia (DRG). Results: No differences in axonal outgrowth were observed between strains, but the number of apoptotic Schwann cells in the injured distal nerve end was higher in DA.Vra1 than in 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) were 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 than in DA rats in injured nerves (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 than DA rats. Discussion: Results highlight the complexity of nerve injury and repair, supporting further investigation of Gsta4 in nerve regeneration.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apoptosis, ATF3, c-Jun, cleaved caspase 3, Hspb1, nerve injury, nerve regeneration, Vra1
in
Frontiers in Cell and Developmental Biology
volume
13
article number
1536347
publisher
Frontiers Media S. A.
external identifiers
  • scopus:105004745955
  • pmid:40356597
ISSN
2296-634X
DOI
10.3389/fcell.2025.1536347
language
English
LU publication?
yes
id
6e1a971c-4c73-4243-a097-0f3709462484
date added to LUP
2025-09-16 16:05:37
date last changed
2025-10-14 19:37:40
@article{6e1a971c-4c73-4243-a097-0f3709462484,
  abstract     = {{<p>Introduction: The rat Vra1 locus, containing glutathione S-transferase alpha 4 (Gsta4), regulates the degeneration of central nervous system (CNS) neurons in toxin-, protein-, and injury-based models. We hypothesize that Piebald Virol Glaxo.1AV1 (PVG) alleles in Vra1 confer protection and increased axonal outgrowth after peripheral nerve injury and repair. Methods: DA rats (n = 14) and DA rats with PVG alleles in the Vra1 locus (DA.Vra1, n = 14) were subjected to sciatic nerve transection and immediate repair. After 6 days, axonal outgrowth and protein and gene expression were analyzed in injured and uninjured nerves and dorsal root ganglia (DRG). Results: No differences in axonal outgrowth were observed between strains, but the number of apoptotic Schwann cells in the injured distal nerve end was higher in DA.Vra1 than in 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) were 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 than in DA rats in injured nerves (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 than DA rats. Discussion: Results highlight the complexity of nerve injury and repair, supporting further investigation of Gsta4 in nerve regeneration.</p>}},
  author       = {{Stenberg, Lena and Jewett, Michael and Dueñas Rey, Alfredo and Swanberg, Maria and Dahlin, Lars B.}},
  issn         = {{2296-634X}},
  keywords     = {{apoptosis; ATF3; c-Jun; cleaved caspase 3; Hspb1; nerve injury; nerve regeneration; Vra1}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Cell and Developmental Biology}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.3389/fcell.2025.1536347}},
  doi          = {{10.3389/fcell.2025.1536347}},
  volume       = {{13}},
  year         = {{2025}},
}