ASSEMBLY OF PROTEINS TO POSTSYNAPTIC DENSITIES AFTER TRANSIENT CEREBRAL-ISCHEMIA

Transient ischemia leads to changes in synaptic efficacy and results i n selective neuronal damage during the postischemic phase, although th e mechanisms are not fully understood. The protein composition and ult rastructure of postsynaptic densities (PSDs) were studied by using a r at transient ischemic model. We found that a brief ischemic episode in duced a marked accumulation in PSDs of the protein assembly ATPases, N -ethylmaleimide-sensitive fusion protein, and heat-shock cognate prote in-70 as well as the BDNF receptor (trkB) and protein kinases, as dete rmined by protein microsequencing. The changes in PSD composition were accompanied by a 2.5-fold increase in the yield of PSD protein relati ve to controls. Biochemical modification of PSDs correlated well with an increase in PSD thickness observed in vivo by electron microscopy. We conclude that a brief ischemic episode modifies the molecular compo sition and ultrastructure of synapses by assembly of proteins to the p ostsynaptic density, which may underlie observed changes in synaptic f unction and selective neuronal damage.