Increased cutaneous NGF and CGRP-labelled trkA-positive intra-epidermal nerve fibres in rat diabetic skin
Autor: | Alison R. Loescher, David Andrew, Peter G. Robinson, Laura J Evans, Fiona M. Boissonade |
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Rok vydání: | 2012 |
Předmět: |
Male
medicine.medical_specialty Calcitonin Gene-Related Peptide Immunocytochemistry Enzyme-Linked Immunosorbent Assay Tropomyosin receptor kinase A Calcitonin gene-related peptide Diabetes Mellitus Experimental Rats Sprague-Dawley Nerve Fibers Internal medicine Diabetes mellitus Nerve Growth Factor medicine Animals Receptor trkA Skin integumentary system business.industry General Neuroscience Streptozotocin medicine.disease Rats Disease Models Animal Endocrinology Nerve growth factor nervous system Calcitonin Neuropathic pain business Ubiquitin Thiolesterase medicine.drug |
Zdroj: | Neuroscience Letters. 506:59-63 |
ISSN: | 0304-3940 |
DOI: | 10.1016/j.neulet.2011.10.049 |
Popis: | In this study we have determined the amount of Nerve Growth Factor (NGF) and the innervation density of the glabrous hindpaw skin of diabetic rats (n=4) and controls (n=3). The proportion of intra-epidermal nerve fibres (IENF) expressing the high affinity NGF receptor (trkA) and calcitonin gene-related peptide (CGRP) were also determined. Four weeks after induction of diabetes by intraperitoneal streptozotocin injection skin was analyzed for: (i) NGF content using ELISA and (ii) the innervation density of peptidergic afferents that also expressed trkA using immunocytochemistry. NGF levels were approximately three-fold higher in diabetic skin compared to controls (diabetic: 134.7±24.0 (SD) pgml(-1), control: 42.7±21.5pgml(-1), p=0.002). As expected there was a significant reduction in IENF density in diabetic skin (2.7±1.3 fibresmm(-1)) compared to controls (6.9±1.5 fibresmm(-1); p=0.01). In diabetic rats there was no significant difference in the proportion of trkA-labelled IENF (diabetic 74±21%; control 83±15%, p=0.6), but significantly more trkA-positive IENF were also labelled by CGRP antibodies in diabetic skin compared to controls (diabetic 89±22%; control 38±2%, p=0.03). These data suggest that in diabetes the upregulation of cutaneous NGF may 'over-troph' the surviving axons, increasing CGRP labelling, which may be important in the aetiology of painful diabetic neuropathy. |
Databáze: | OpenAIRE |
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