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 axotomy and selectively up-regulate the transcription factor c-Jun. In the present study we investigated whether these cells concomitantly up-regulate the growth-associated protein-43 (GAP-43), a potential target gene of c-Jun implicated in axonal growth and regeneration. Using in situ hybridization histochemistry (ISHH) it was demonstrated that postlesional c-jun mRNA expression is accompanied by an increased expression of GAP-43 mRNA in the medial septum 3 days following fimbria-fornix transection (FFT). The increase reached a maximum at 7 days and gradually declined thereafter (17 days, 3 weeks). Retrograde prelabeling with Fluoro-Gold followed by axotomy and ISHH revealed that GAP-43 mRNA was up-regulated in septohippocampal projection neurons. Colocalization of GAP-43 mRNA and choline acetyltransferase protein showed that GAP-43 mRNA was expressed by cholinergic medial septal neurons after axotomy. Selective immunolesioning of the cholinergic component of the septohippocampal projection with 192 IgG-saporin followed by FFT demonstrated that GAP-43 mRNA was also synthesized by axotomized GABAergic neurons. These results demonstrate an up-regulation of GAP-43 mRNA in axotomized septohippocampal 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-43 in lesioned medial septal neurons that may contribute to their survival and regenerative potential following axotomy.
Haas
C A
CA
Institute of Anatomy I, University of Freiburg, PO Box 111, D-79001 Freiburg, Germany. haascaro@uni-freiburg.de
Hollerbach
E
E
Deller
T
T
Naumann
T
T
Frotscher
M
M
D000818:Animals; D019771:Axotomy; D020712:Fornix, Brain / Q000502:physiology*; D019922:GAP-43 Protein / Q000235:genetics*; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020665:Septum of Brain / Q000166:cytology / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic
D019922:GAP-43 Protein; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger