p75 neurotrophin receptor expression is induced in apoptotic neurons after seizure

Abstract

Seizure causes neuronal cell loss in both animal models and human epilepsy. To determine the contribution of apoptotic mechanisms to seizure- induced neuronal cell death, rat brains were examined for the occurrence of terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)- positive 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 that the vast majority of TUNEL-positive cells were neurons. To identify components of the signal transduction cascade promoting postseizure apoptosis, the expression of the p75 neurotrophin receptor (p75NTR) was examined. Seizure-induced increases in p75NTR protein and mRNA were detected in hippocampus, piriform cortex, and entorhinal cortex. Immunohistochemical double labeling revealed almost complete correspondence between TUNEL- positive and p75NTR-expressing cells, suggesting that seizure-induced neuronal loss within the CNS occurs through apoptotic signaling cascades involving p75NTR.