Speaker: Dr. William J. Costain National Research Council of Canada-Institute for Biological Sciences, Canada Proteomic and glycomic exploration of the ischemic synapse reveals systematic disturbances implicated in neuronal cell death Central nervous system neurons are highly susceptible to ischemic damage. Cerebral ischemia is known to induce numerous alterations in gene and protein expression that are involved in mediating neuronal cell death and brain remodeling. Additionally, cerebral ischemia induces dramatic and transiently reversible structural changes in dendritic spine morphology that precede delayed post-ischemic neuronal death. This suggests that synaptic stress may initiate signals that propagate toward the cell body and instigate delayed cell death through a process described as ‘synaptic apoptosis’. Many neuroprotection strategies have targeted synaptic receptors and ion channels involved in mediating signaling. While much work has been done to exploit the therapeutic potential of modulating synaptic signaling, to date there have been no systematic studies of the effect of cerebral ischemia on the synaptic proteome and glycome. Our work is primarily focused on characterizing ischemia-induced proteomic and glycomic changes in the isolated synaptosome. I will describe some of our recent work examining the effect of cerebral ischemia on synaptic adhesion molecules expression and its physiological implications. Additionally, I will describe our efforts to characterize the proteomic response of the ischemic synaptosome. I will also describe our novel approach to assessing ischemia-induced alterations in protein glycosylation. Our approach to the problem of cerebral ischemia has allowed us to identify a number of novel synaptic proteomic and glycomic phenomena that have demonstrated that cerebral ischemia induces systematic disruption of normal synaptic, organelle and cellular function.