Medial septal cholinergic neurons express c-Jun but do not undergo DNA fragmentation after fornix-fimbria transections

Abstract

We investigated the expression of inducible transcription factors (ITFs) and the fate of medial septal (MS) cholinergic neurons following fornix fimbria (FF) transection. c-Jun, but not c-Fos or Krox 24 was induced in nerve growth factor receptor-immunoreactive (NGFr-ir), parvalbumin-negative MS neurons by 48 h and still highly expressed 2 months after transection. JunD was expressed only at 48 h after transection. Levels of choline acetyl transferase immunoreactivity (ChAT-ir) and NGFr-ir decreased substantially 7 and 14 days respectively following FF transection and remained depressed for up to 2 months. We also investigated other measures of nerve cell death and found that there was a time-dependent loss of cresyl violet staining, but no evidence of DNA fragmentation, acidophilia or clusterin expression in the MS region. There was however, good evidence of microglial activation and astrocyte hypertrophy in the MS. These results suggest that axotomized c-Jun-positive septohippocampal neurons lose their cholinergic phenotype but do not die for up to 2 months after FF transection. The function of c-Jun in axotomized MS neurons remains a mystery, but c-Jun expression alone is clearly not sufficient to elicit death of these neurons.