Up-regulation of growth-associated protein 43 mRNA in rat medial septum neurons axotomized by fimbria-fornix transection

Transection of septohippocampal fibres is widely used to study the response of CNS neurons to axotomy. Septohippocampal projection neurons survive axo tomy and selectively up-regulate the transcription factor c-Jun. In the pre sent study we investigated whether these cells concomitantly up-regulate th e growth-associated protein-43 (GAP-43), a potential target gene of c-Jun i mplicated in axonal growth and regeneration. Using in situ hybridization hi stochemistry (ISHH) it was demonstrated that postlesional c-jun mRNA expres sion is accompanied by an increased expression of GAP-43 mRNA in the medial septum 3 days following fimbria-fornix transection (FFT). The increase rea ched a maximum at 7 days and gradually declined thereafter (17 days, 3 week s). Retrograde prelabeling with Fluoro-Gold followed by axotomy and ISHH re vealed that GAP-43 mRNA was upregulated in septohippocampal projection neur ons. Colocalization of GAP-43 mRNA and choline acetyltransferase protein sh owed that GAP-43 mRNA was expressed by cholinergic medial septal neurons af ter axotomy. Selective immunolesioning of the cholinergic component of the septohippocampal projection with 192 IgG-saporin followed by FFT demonstrat ed that GAP-43 mRNA was also synthesized by axotomized GABAergic neurons. T hese results demonstrate an up-regulation of GAP-43 mRNA in axotomized sept ohippocampal projection neurons independent of their transmitter phenotype which is closely correlated with c-Jun expression. Because the GAP-43 gene contains an AP-1 site, we hypothesize a c-Jun-driven up-regulation of GAP-4 3 in lesioned medial septal neurons that may contribute to their survival a nd regenerative potential following axotomy.