Journal of Neuroscience, Vol 16, 1894-1903, Copyright © 1996 by Society for Neuroscience
Selective expression of the immediate early gene c-jun in axotomized rat medial septal neurons is not related to neuronal degeneration
CA Haas, T Deller, T Naumann and M Frotscher
Institute of Anatomy, University of Freiburg, Germany.
In the present study, we use the anatomically well defined septohippocampal
projection to study the molecular events involved in the reaction of
neurons to axotomy. The expression of three immediate early genes (c-fos,
c-jun, and jun B) was investigated in rat septohippocampal neurons after
axotomy by bilateral fimbria-fornix transection (FFT). Moreover, the extent
of retrograde degeneration in the septal complex was assessed by analyzing
DNA fragmentation. In a postoperative time course analysis, a strong
increase of c-jun immunoreactivity (IR) was observed in the nuclei of
neurons in the medial septum/diagonal band complex (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 disappeared. The
c-jun-positive MS neurons were identified as former septohippocampal
projection cells by double-labeling with the retrogradely 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 IR were not detectable in
either unoperated or lesioned medial septal neurons. Experiments using the
TdT-mediated deoxyuridine triphosphate nick-end-labeling technique,
designed to detect nuclear DNA fragmentation in degenerating neurons,
complemented this study. During the postoperative time range studied, MS
neurons did not exhibit DNA fragmentation. We conclude that MSDB neurons
survive axotomy by FFT and display characteristic changes in gene
expression.