Effect of Streptozotocin‐induced Diabetes on Ngf, P75(ntr) and Trka Content of Prevertebral and Paravertebral Rat Sympathetic Ganglia

Abstract

Diabetic autonomic neuropathy results in significant morbidity and mortality. Both diabetic humans and experimental animals show neuroaxonal dystrophy of autonomic nerve terminals, particularly in the prevertebral superior mesenteric ganglia (SMG) and celiac ganglia (CG) which innervate the hyperplastic/hypertrophic diabetic small intestine. Previously, investigators suggested that disturbances in ganglionic nerve growth factor (NGF) content or transport might play a pathogenetic role in diabetic autonomic pathology. To test this hypothesis, we measured NGF content and NGF receptor expression, p75(NTR) (low affinity neurotrophin receptor) and trkA (high affinity NGF receptor), in control and diabetic rat SMG, CG and superior cervical ganglia (SCG). Surprisingly, rather than a decrease, we observed an approximate doubling of NGF content in the diabetic SMG and CG, a result which reflects increased NGF content in the hyperplastic diabetic alimentary tract. No change in NGF content was detected in the diabetic SCG which is relatively spared in experimental diabetic autonomic neuropathy. NGF receptor expression was not consistently altered in any of the autonomic ganglia. These observations suggest that increased NGF content in sympathetic ganglia innervating the diabetic alimentary tract coupled with intact receptor expression may produce aberrant axonal sprouting and neuroaxonal dystrophy.

Nerve Growth Factor and Diabetic Neuropathy

“…Transgenic studies have shown that in development trk A receptor mediates neuronal survival by blocking apoptotic p75 signals (Majdan et al, 2001), emphasizing the importance of p75 interaction with trk neurotrophin receptors. Alternatively, it has been demonstrated that there is a reduction in expression of p75 in the autonomic ganglia of STZ-diabetic rats (Schmidt et al, 2000), reducing NGF signaling into the neurons. Regardless of mechanism, it is apparent that the low-affinity neurotrophin receptor is essential to the integrity of small nerve fibers involved in pain, warm thermal perception, and sweating and as such, constitute an important target for corrective therapy in diabetic neuropathy.…”