ffect of hyperglycemia on Neuregulin 1, ErbB4 and Syntaxin-1 Expression in Spinal Cord of Streptozotocin Induced Diabetic Rats and C6 Cell Line

Abstract

Diabetes is a common metabolic disorder wherein the body’s ability to either produce or respond to insulin is impaired resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood. Hyperglycaemia is a condition in which blood glucose levels are abnormally high that may exceed 200 mg/dl and can cause complications like Diabetic neuropathy which is caused as a result of activation of certain abnormal metabolic pathways. Diabetic Neuropathy affects both Central and Peripheral Nervous System. Spinal cord has a major role in nerve impulse propagation, integration of information, reflexes and movement. Diabetic neuropathy leads to motor dysfunction due to activation of DAG/PKC pathway that results in ischemia, hypoxia and vasoconstriction that causes damage to lower motor neurons. The NRG1/ErbB4 signalling pathway is involved in survival, proliferation, differentiation, regeneration of neurons. Here we have assessed the changes in levels of NRG1, ErbB4 and Syntaxin-1 in spinal cord of Diabetic rats. Syntaxin-1 has a role in vesicle exocytosis and has been taken for study as a marker of synaptic plasticity. It was observed that gene expression levels of NRG1 were low in spinal cord tissue in hyperglycaemic conditions while ErbB4 and syntaxin-1 was upregulated. We concluded that NRG1 although had low expression levels, it could still bind to ErbB4 leading to a certain level of activation of the regeneration pathway due to the body’s innate homeostatic mechanism. This down regulation of the NRG1-ErbB4 signalling pathway in the lower motor neurons of the lumbar region of the spinal cord could be a possible cause of motor dysfunction. In-vitro studies revealed down regulation in expression of all three genes from which we can conclude that regeneration does not occur in C6 glial cells due to absence of any innate body homeostasis and more oxidative stress that results in altered DNA methylation pattern, which in turn leads to altered gene expression levels.