18-LB: Histone Modifications and CXCR4 Chemokine Receptor Signaling in Hyperglycemic DRG Neurons

Abstract

Diabetes is a global epidemic that affects many individuals throughout the world and presents a major health challenge to society. The state of chronic hyperglycemia can have many devastating secondary effects including neuropathy, nephropathy, retinopathy, and cardiovascular disease. The diabetes mediated neuropathic complications are a substantial burden to society due to a lack of therapies as well as decreased quality of life and increased mortality. Approximately 50% diabetic patients suffer from neuropathy which is described as alterations of pain sensation in the feet that leads to increased risk for infection, ulcers, non-traumatic amputations and ultimately death. Painful diabetic neuropathy (PDN) affects individuals within 20 years after the onset of disease, mediated by the gradual degeneration of axonal structures in sensory neurons. It is known that hyperglycemia is involved in the pathogenesis of this disease, but specific mechanisms are not well understood. Previous studies have shown that inflammation and epigenetic changes may play a role in the development of PDN. Specifically, it has been demonstrated that the chemokine receptor CXCR4 is involved in inflammation relating to PDN while the histone deacetylases HDAC4 and HDAC6 are involved in mediating the epigenetic changes in sensory neurons under hyperglycemic conditions. This study investigated the alterations in inflammatory mediators and epigenetic changes in sensory neurons under normal glucose and high glucose environments. Western blot and immunocytochemistry techniques were used to measure any differences in these two conditions. The results from this study demonstrated an upregulation of histone deacetylases and CXCR4 in hyperglycemic conditions, while histone acetyltransferases were shown to be down-regulated in high glucose environments. These findings may lead to potential therapeutic targets for PDN since it is a life altering condition with minimal treatment options available today. Disclosure N. Satterfield: None. V. Thakur: None. M. Chattopadhyay: None. Funding Texas Tech University Health Sciences Center El Paso (183381SEED)