| OCR Text |
Show THE UNIVERSITY OF UTAH HONORS COLLEGE ROLE OF PGF2A FP RECEPTOR AGAINST EXCITOTOXC INSULT IN OLIGODENDROCYTE PRECURSOR CELLS Satya Bellamkonda, (Noel Carlson) Department of Bioengineering Department of Neurobiology and Anatomy University of Utah Multiple Sclerosis is a demyelinating disease of the central nervous system, for which treatment options are limited. In MS, the myelin-producing cells, oligodendrocytes and their precursor cells (OPCs), die in the disease progression due in part to excitotoxic death. Neurotransmitters activate ion channels, exciting the cells to death. In addition, extracellular ATP can also act on other receptors (called P2X7) and cause excitotoxic death. Inhibition of cyclo-oxygenase- 2 (COX-2) has been shown to protect OPCs from excitotoxic death. COX-2 is the rate-limiting step in the production of several prostaglandins. W e have demonstrated that one of these prostaglandins, PGF2a, and its associated FP receptor are found in OPCs. W e hypothesized that inhibiting the FP receptor would protect OPCs from excitotoxic death. W e tested this using dispersed O P C cultures in vitro which were prepared from mice. The cultures were treated with glutamate receptor agonist kainic acid (KA) or P2X7 receptor agonist BzATP. The cultures were co-treated with FP antagonist AL 8810 with and without excitotoxic stimulation (KA or BzATP). Viability of OPCs was assessed 24 hours after treatment. The FP antagonist protected OPCs from both KA-induced excitotoxicity (p<0.05) and BzATP-induced excitotoxic-ity (p<0.01). These results identify the FP receptor as an important modulator of O P C survival against excitotoxic insult and m a y be an important target for future therapies in MS. Satya Bellamkonda Noel Carlson |
