Effect of ERK inhabitation on diabetric neuropathy in rats

Abstract

Introduction: Diabetic neuropathy is a major chronic complication of diabetes and the most important cause of non-traumatic amputation of the lower extremity. Several functional and structural abnormalities have been observed: impaired nerve conduction, demyelination and axon degeneration. The previous studies have shown that ERK, a member of mitogen-activated protein kinase (MAPK) family, was activated in primary sensory neurons cultured in high glucose condition and its inhibition resulted in decreased neuronal death. According to the above evidence, it is possible that the activation of ERK plays a deleterious role in diabetic neuropathy. However, its effect has not been studied. Objective: Therefore, the main objective of this project was to examine the effect of ERK inhibition on structural abnormalities of peripheral nerve in diabetic rats. Methods: Diabetes was induced by a single ip. Injection of STZ 55 mg/kg and the diabetic rats were randomly divided into 2 groups: vehicle (DV) and inhibitor (DI). The inhibitor of ERK (u0126) 300 ug/kg/day was given ip. From week 5 after the onset of diabetes until week 7 The study on sciatic nerve conduction velocity was done in the DV and DI groups as well as in the control © group. Subsequently, the rats were sacrificed and sciatic nerve and L4-5 dorsal root ganglion (DRG) were removed for western blot analyses and structural. Results: The DV and DI groups had significant weight loss, hyperglycemia and slowing conduction velocity of sciatic nerve compared with the C group. However, there were no significant differences in these parameters between the DV and DI groups. The phosphorylation of ERK was in DRG from diabetic rats. However, the level of phosphorylation in the DI was lower than the DV groups. The structural analysis increased the showed a trend toward axonal shrinkage and a significant decrease in myelin thickness in sciatic nerve of diabetic rats without any difference between the DV and DI groups. Conclusion: u0126 can reduce the level of ERK phosphorylation (ERK-P) in the DRG of diabetic rats. However, it appears that the ERK inhibition did not affect neurophysiological and structural abnormalities in the experimental diabetic neuropathy. To obtain a precise conclusion, future studies with earlier start or longer duration of treatment are needed.