Induction of p75NGFR in human diabetic neuropathy

In this immunohistochemical study we investigated the expression of low-affinity NGF receptor (p75NGFR) in peripheral nerves from 16 patients with type I or type II diabetes mellitus. Fourteen nerves from age- and sex-matched normal individuals and nine nerves from non-diabetic patients with ischemic neuropathy served as controls. All nerve samples were preliminarily examined by standard histology, fiber teasing and electron microscopy. Increased p75NGFR immunoreactivity was detectable within the endoneurium of cross-sections from ischemic and particularly from diabetic nerves. Immuno-teasing demonstrated that p75NGFR immunostaining was distributed along the entire length of isolated nerve fibers undergoing axonal degeneration. Quantitative assessment of p75NGFR immunoreactivity, performed by histospectrophotometry and expressed as percentage of adsorbance, was 21.20 +/- 3.50 in nerves from diabetic patients, 13.35 +/- 3.62 in nerves from non-diabetic patients with ischemic neuropathy and 9.02 +/- 2.75 in normal controls. The increased expression of p75NGFR in diabetic nerves is consistent with an axonopathic defect and further suggests involvement of NGF and other neurotrophins in the pathogenesis of human diabetic neuropathy.