Meeting Abstract

P1.118  Thursday, Jan. 3  RAGE-mediated neuronal outgrowth in a model diabetic system. LIU, Jane Z.*; JACKSON, Annise K.; SCHMIDT, Ann Marie; GEDDIS, Matthew S.; Columbia University, NY, NY; Columbia University, NY, NY; Columbia University, NY, NY; Columbia University, NY, NY jzl2103@columbia.edu

The Receptor for Advanced Glycation Endproducts (RAGE) is a multiligand receptor of the immunoglobulin superfamily that has been implicated in the complications that arise from diabetes and subsequently RAGE signaling has been associated with accelerated disease conditions in most body systems. In the nervous system, however, the inhibition of RAGE signaling after injury has been shown to decrease neuronal regeneration. Transgenic mice expressing a dominant-negative signaling-deficient form of RAGE in macrophages and neurons showed a decrease in neuronal regeneration in comparison to wild type mice after sciatic nerve crush. This suggests that RAGE signaling may have an inherent role in regeneration. In the following study, we have examined the basic hypothesis that RAGE signaling increases neuronal regeneration in vitro. Dorsal root ganglion (DRGs) neurons were isolated from 3-week old wild-type and RAGE -/- mice and plated on collagen-coated tissue culture dishes. Neurons were then observed neurite projection number and outgrowth rate over a time course of 1 hour at 10 minute intervals. RAGE activation was then induced by the ligands s100b and CML-AGEs (to simulate euglycemic and hyperglycemic conditions) and observed an additional hour at 10 minute intervals. Neuronal survival was also examined up to 7 days after ligand exposure. Measurements revealed that exposure to RAGE ligands is at first beneficial and then detrimental suggesting that RAGE has a complex role in neuronal regeneration. Further experiments are designed to elucidate the pathway and timing of RAGE-mediated neuronal regeneration. Supported by: NIH grant AG17490.