Neurotrophin-3 is increased in skin in human diabetic neuropathy.
Neurotrophin-3 (NT-3), a member of the neurotrophin family, has been shown to be necessary for the development of muscle spindle and Merkel cell afferent nerve fibres in animal models. The presence of NT-3 in the suprabasal epidermis, where many unmyelinated sensory fibres terminate, has been shown for the first time. As these fibres are affected in early diabetic neuropathy and a clinical trial of recombinant human NT-3 in diabetic neuropathy is in progress, the concentrations of endogenous NT-3 in skin of 24 patients at different stages of diabetic polyneuropathy have been investigated. NT-3 concentrations, measured with a specific immunoassay, were significantly higher in affected skin biopsies from patients with diabetic neuropathy than matched control skin (diabetic skin 6.32 (1.18) pg/mg v control skin 1.28 (0.05) (mean (SEM)); p<0.004, Mann-Whitney U test), particularly in the later stages. The optical density of NT-3-immunostaining was also significantly greater in the epidermis in diabetic patients (diabetic epidermis 0.30 (0.06) v controls 0.24 (0.01); p<0.02). No correlation was found between individual quantitative sensory tests and the increase of NT-3 concentration. The increase of NT-3 seems to reflect the degree of skin denervation in diabetic neuropathy, and may represent a compensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.
Kennedy
A J
AJ
Academic Department of Neurology, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
Wellmer
A
A
Facer
P
P
Saldanha
G
G
Kopelman
P
P
Lindsay
R M
RM
Anand
P
P
D000328:Adult; D001706:Biopsy; D003929:Diabetic Neuropathies / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009414:Nerve Growth Factors / Q000032:analysis*; D020933:Neurotrophin 3; D012016:Reference Values; D011984:Sensory Receptor Cells / Q000473:pathology*; D012867:Skin / Q000294:innervation* / Q000473:pathology
D009414:Nerve Growth Factors; D020933:Neurotrophin 3