p75 neurotrophin receptor expression is induced in apoptotic neurons afterseizure

Seizure causes neuronal cell loss in both animal models and human epilepsy. To determine the contribution of apoptotic mechanisms to seizure-induced n euronal cell death, rat brains were examined for the occurrence of terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positi ve nuclei after pilocarpine-induced seizure. Numerous TUNEL-positive cells were observed throughout the postseizure hippocampus, piriform cortex, and entorhinal cortex. Combined TUNEL/NeuN immunocytochemistry demonstrated tha t the vast majority of TUNEL-positive cells were neurons. To identify compo nents of the signal transduction cascade promoting postseizure apoptosis, t he expression of the p75 neurotrophin receptor (p75NTR) was examined. Seizu re-induced increases in p75NTR protein and mRNA were detected in hippocampu s, piriform cortex, and entorhinal cortex. Immunohistochemical double label ing revealed almost complete correspondence between TUNEL-positive and p75N TR-expressing cells, suggesting that seizure-induced neuronal loss within t he CNS occurs through apoptotic signaling cascades involving p75NTR.