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 activation following excitotoxin challenge. To determine whether PAF receptor (PAFR) expression is altered during excitotoxicity, changes in PAFR mRNA localization were compared with markers of neuronal apoptosis and reactive gliosis following systemic injection of kainic acid. Data from semi-quantitative RT-PCR, in situ hybridization, DNA fragmentation, cellular morphology analysis, and immunohistochemistry demonstrate that the localization of PAFR mRNA is altered during kainic acid-induced neurodegeneration. While PAFR mRNA is normally exhibited by neurons and microglia in rat hippocampus, expression becomes restricted to apoptotic neurons and to glia involved in phagocytosing apoptotic debris following treatment with excitotoxin. PAFR mRNA is rarely detected in surviving neurons. These data provide the first indication that PAFR-expressing neurons may be preferentially susceptible to excitotoxic challenge.
Bennett
S A
SA
Institute of Biochemistry, Life Science Research Centre, Carleton University, Ottawa, Ontario, K1S 5B6, Canada. stefbenn@ccs.carleton.ca
Chen
J
J
Pappas
B A
BA
Roberts
D C
DC
Tenniswood
M
M
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000473:pathology; D002470:Cell Survival; D005786:Gene Expression Regulation / Q000187:drug effects; D005911:Gliosis; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects
D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D007608:Kainic Acid