PLATELET-ACTIVATING-FACTOR RECEPTOR EXPRESSION IS ASSOCIATED WITH NEURONAL APOPTOSIS IN AN IN-VIVO MODEL OF EXCITOTOXICITY

Platelet activating factor (PAF), an endogenous proinflammatory agent, mediates neuronal survival, glutamate release, and transcriptional ac tivation following excitotoxin challenge. To determine whether PAF rec eptor (PAFR) expression is altered during excitotoxicity, changes in P AFR mRNA localization were compared with markers of neuronal apoptosis and reactive gliosis following systemic injection of kainic acid. Dat a from semi-quantitative RT-PCR, in situ hybridization, DNA fragmentat ion, cellular morphology analysis, and immunohistochemistry demonstrat e that the localization of PAFR mRNA is altered during kainic acid-ind uced neurodegeneration. While PAFR mRNA is normally exhibited by neuro ns and microglia in rat hippocampus, expression becomes restricted to apoptotic neurons and to glia involved in phagocytosing apoptotic debr is following treatment with excitotoxin. PAFR mRNA is rarely detected in surviving neurons. These data provide the first indication that PAF R-expressing neurons may be preferentially susceptible to excitotoxic challenge.