Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome.
Growth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patien...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0277133 |
| _version_ | 1797959519561580544 |
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| author | Liam Carroll Oliver Sandy-Hindmarch Georgios Baskozos Guan Cheng Zhu Julia McCarthy Annina Schmid |
| author_facet | Liam Carroll Oliver Sandy-Hindmarch Georgios Baskozos Guan Cheng Zhu Julia McCarthy Annina Schmid |
| author_sort | Liam Carroll |
| collection | DOAJ |
| description | Growth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patients with peripheral neuropathies; with several studies showing a reduction in GAP-43 immunoreactive cutaneous nerve fibres. However, it remains elusive whether cutaneous GAP-43 is a valid marker for human nerve regeneration. Here, we present a cohort of 22 patients with electrodiagnostically confirmed carpal tunnel syndrome (CTS), used as a model system for focal nerve injury and neural regeneration after decompression surgery. We evaluate GAP-43 immunoreactivity and RNA expression levels in finger skin biopsies taken before and 6 months after surgery, relative to healthy controls. We further classify patients as 'regenerators' or 'non-regenerators' based on post-surgical epidermal re-innervation. We demonstrate that patients with CTS have lower GAP-43 positive intra-epidermal nerve fibre density (IENFD) before surgery than healthy controls. However, this difference disappears when normalising for total IENFD. Of note, we found surgery did not change GAP-43 expression in IENF, with no differences both in patients who were classified as regenerators and non-regenerators. We also did not identify pre-post surgical differences in cutaneous GAP-43 gene expression or associations with regeneration. These findings suggest cutaneous GAP-43 may not be a compelling marker for nerve regeneration in humans. |
| first_indexed | 2024-04-11T00:33:58Z |
| format | Article |
| id | doaj.art-9ae8c39fa852484896383ae691cbe7e1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T00:33:58Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9ae8c39fa852484896383ae691cbe7e12023-01-07T05:31:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011711e027713310.1371/journal.pone.0277133Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome.Liam CarrollOliver Sandy-HindmarchGeorgios BaskozosGuan Cheng ZhuJulia McCarthyAnnina SchmidGrowth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patients with peripheral neuropathies; with several studies showing a reduction in GAP-43 immunoreactive cutaneous nerve fibres. However, it remains elusive whether cutaneous GAP-43 is a valid marker for human nerve regeneration. Here, we present a cohort of 22 patients with electrodiagnostically confirmed carpal tunnel syndrome (CTS), used as a model system for focal nerve injury and neural regeneration after decompression surgery. We evaluate GAP-43 immunoreactivity and RNA expression levels in finger skin biopsies taken before and 6 months after surgery, relative to healthy controls. We further classify patients as 'regenerators' or 'non-regenerators' based on post-surgical epidermal re-innervation. We demonstrate that patients with CTS have lower GAP-43 positive intra-epidermal nerve fibre density (IENFD) before surgery than healthy controls. However, this difference disappears when normalising for total IENFD. Of note, we found surgery did not change GAP-43 expression in IENF, with no differences both in patients who were classified as regenerators and non-regenerators. We also did not identify pre-post surgical differences in cutaneous GAP-43 gene expression or associations with regeneration. These findings suggest cutaneous GAP-43 may not be a compelling marker for nerve regeneration in humans.https://doi.org/10.1371/journal.pone.0277133 |
| spellingShingle | Liam Carroll Oliver Sandy-Hindmarch Georgios Baskozos Guan Cheng Zhu Julia McCarthy Annina Schmid Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome. PLoS ONE |
| title | Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome. |
| title_full | Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome. |
| title_fullStr | Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome. |
| title_full_unstemmed | Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome. |
| title_short | Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome. |
| title_sort | cutaneous expression of growth associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome |
| url | https://doi.org/10.1371/journal.pone.0277133 |
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