In neurodegenerative disorders, oxidative stress is an important mediator of neural cell death. However, very little is known about the effects of oxidative stress on the cells critical for the development, maintenance and repair of the CNS: the neural stem cells (NSC). We hypothesize that oxidative stress induces the expression of immune recognition molecules on the surface of NSCs, which makes them vulnerable targets for rejection or destruction. We are currently investigating this hypothesis by first, examining whether oxidative stress affects the expression of immune molecules in NSC. We are currently using the mouse C17.2 NSC line for these in vitro studies. We have found that model NSCs express the Fas (CD95) death receptor and B7.1 co-stimulatory molecule, and that hydrogen peroxide up regulates their expression. Further flow cytometry experiments indicate the up regulation of co-stimulatory molecule B7.1 in response to oxidative stress induced by rotenone, a neurotoxic pesticide. Secondly, we will determine whether protection from reactive oxygen intermediates promotes NSC's survival and differentiation following oxidative stress. We are examining mitochondrial uncoupling protein 2 (UCP-2), a protein which is known to increase cells' anti-oxidative capacity and reduce expression of immune recognition molecules. As UCP-2 enhances the capacity to handle reactive oxygen species inside mitochondria, we believe that UCP-2 expression will reduce the effects of oxidative stress. To this end, we are developing a C17.2 cell line stably transfected with a construct containing a constitutively expressed mouse UCP-2 gene. Thus, we have found that oxidative stress affects the dynamics of NSC immune molecule expression and we are investigating possible protection from such stress via UCP-2.