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
(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.
(Less)
- author
- Stenberg, Lena
LU
; Jewett, Michael ; Dueñas Rey, Alfredo LU ; Swanberg, Maria LU and Dahlin, Lars B. LU
- organization
- publishing date
- 2025
- 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
-
- pmid:40356597
- scopus:105004745955
- 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
- 2025-09-30 17:46:04
@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}}, }