NERVE GROWTH-FACTOR (NGF) AND DIABETIC NEUROPATHY IN THE RAT - MORPHOLOGICAL INVESTIGATIONS OF THE SURAL NERVE, DORSAL-ROOT GANGLION, AND SPINAL-CORD

A number of functions for nerve growth factor (NGF) have been describe d over the past years, including its role for neuronal function and re generation during toxic or metabolic neuropathies. In order to further assess the effects of NGF on the somatosensory system in diabetic neu ropathy, the sural nerve, dorsal root ganglia (DRG), and dorsal horn o f the spinal cord were investigated by morphological and quantitative methods in rats after 12 weeks of uncontrolled streptozotocin-induced diabetes mellitus. The results from our study suggest a twofold effect of NGF: (1) In sural nerve treatment with NGF (0.1 or 0.5 mg/kg) for 12 weeks was able to reverse distinct diabetes-related alterations in myelinated nerve fiber morphology, such as myelin thickness. These cha nges occured in the entire myelinated population of sensory nerves and were not restricted to nociceptive nerve fibers. (2) The NGF effect o n neurotransmitters of the sensory, nociceptive system was reflected b y increased CG;RP and substance P content in the DRG and in the dorsal horn of the spinal cord. No change of trkA receptor immunostaining wa s seen in DRGs of diabetic rats; however, a reduction of trkA immunore activity of DRG neurons was noted after long-term NGF treatment of hea lthy controls. The data demonstrate that NGF regulates a number of neu ronal parameters along peripheral and central parts of the somatosenso ry pathway in the adult. This neurotrophic support may be essential fo r inducing functionally significant regenerative mechanisms in diabeti c neuropathy. (C) 1998 Academic Press.