SELECTIVE EXPRESSION OF THE IMMEDIATE-EARLY GENE C-JUN IN AXOTOMIZED RAT MEDIAL SEPTAL NEURONS IS NOT RELATED TO NEURONAL DEGENERATION

In the present study, we use the anatomically well defined septohippoc ampal projection to study the molecular events involved in the reactio n of neurons to axotomy. The expression of three immediate early genes (c-fos, c-jun, and jun B) was investigated in rat septohippocampal ne urons after axotomy by bilateral fimbria-fornix transection (FFT). Mor eover, the extent of retrograde degeneration in the septal complex was assessed by analyzing DNA fragmentation. In a postoperative time cour se analysis, a strong increase of c-jun immunoreactivity (IR) was obse rved in the nuclei of neurons in the medial septum/diagonal band compl ex (MSDB) 2 and 6 d postaxotomy, which was followed by a decline after 12 d and 3 weeks, respectively. Nine weeks after FFT, c-jun IR had di sappeared. The c-jun-positive MS neurons were identified as former sep tohippocampal projection cells by double-labeling with the retrogradel y transported tracer Fluoro-Gold injected into the hippocampus before axotomy. In line with the immunocytochemical data, there was a massive induction of c-jun mRNA in the axotomized MS neurons as visualized by in situ hybridization histochemistry. c-fos mRNA and c-fos or jun B I R were not detectable in either unoperated or lesioned medial septal n eurons. Experiments using the TdT-mediated deoxyuridine triphosphate n ick-end-labeling technique, designed to detect nuclear DNA fragmentati on in degenerating neurons, complemented this study. During the postop erative time range studied, MS neurons did not exhibit DNA fragmentati on. We conclude that MSDB neurons survive axotomy by FFT and display c haracteristic changes in gene expression.