Protection by neuronal growth factors against hyperglycemia induced changes in rat dorsal root ganglion neurons

Abstract

Peripheral neuropathy is a common complication of diabetes that can affect 50% of the patients. It predisposes the patient to several physiological problems in the lower limbs, which may lead to gangrene and even amputation. Due to its widespread prevalence and serious complications it is important to understand the pathogenesis of diabetic neuropathy, so appropriate therapies can be developed. In this study the pathogenesis of diabetic peripheral neuropathy was investigated in both an in vitro and ex vivo model for this disorder. The effect of hyperglycemia on DRG neurons was investigated by measuring the neuronal stress response, measured by the level of ATF3, neurite outgrowth and neuronal viability. Both models showed an increase in the ATF3-level and a decline in neurite outgrowth. There were no significant changes in the number of apoptotic cells in diabetic rats, compared to control rats. These results indicate that hyperglycemia is indeed a key player in the development of diabetic neuropathy. In the second part of the study the beneficial effects of growth factors was documented. Therefore the effect of Enovin, GDNF and VEGF on the neuronal stress response was investigated. Both the in vitro and ex vivo model for diabetic neuropathy showed that all three growth factors can reduce neuronal stress. Furthermore, addition of ENV, GDNF and VEGF increased the overall neurite outgrowth. This research indicates that all tested growth factors have a protective effect on hyperglycemia-induced changes in cultures of DRG neurons. Therefore these compounds can be considered as possible candidates for the treatment of diabetic peripheral neuropathy. However, further research must me conducted to test the safety and tolerance of these compounds before they can be applied for the treatment of this disorder in human patients.