title: Increased gene expression of growth associated protein-43 in skin of patients with early-stage peripheral neuropathies.
abstract: Growth associated protein-43 (GAP-43) is one of the neural proteins associated with nerve injury that is upregulated after nerve injury. To investigate whether GAP-43 quantification in skin biopsies would differentiate subtypes of peripheral neuropathies, we analyzed GAP-43 expression in skin from the lateral thigh and the distal leg. We prospectively enrolled 130 patients with peripheral neuropathies and compared data with healthy controls. Intraepidermal nerve fiber density (IENFD) was determined using antibodies against protein gene product 9.5 (PGP 9.5); anti-GAP-43 antibodies were applied to visualize regenerating nerve fibers. PGP 9.5 and GAP-43 gene expression was analyzed using qRT-PCR. Patients with neuropathies had a generalized reduction of IENFD and GAP-43 immunoreactive fibers compared to controls (p<0.01). In contrast, cutaneous GAP-43 gene expression was increased in proximal skin in patients (p<0.05), particularly when disease duration was short (<3 years; p<0.01). While fiber density for both markers decreased with age in healthy skin (p<0.01), age-dependent reduction of skin innervation was absent in neuropathies. Diagnostic subgroups and neuropathic pain had no influence on skin innervation. We conclude that peripheral neuropathies lead to an initial increase in GAP-43 gene expression as a potential mechanism of regeneration, which is not sustained in neuropathies of long duration.
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Scheytt
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Riediger
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Braunsdorf
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. Electronic address: ueceyler_n@ukw.de.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Üçeyler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000473:pathology* / Q000503:physiopathology; D012189:Retrospective Studies; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase
keywords: Growth associated protein-43; Intraepidermal nerve fibers; Peripheral neuropathy; Protein gene product 9.5; Skin punch biopsy