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Up‐regulation of growth‐associated protein 43 mRNA in rat medial septum neurons axotomized by fimbria‐fornix transection
Author(s) -
Haas Carola A.,
Hollerbach Ewald,
Deller Thomas,
Naumann Thomas,
Frotscher Michael
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2000.01329.x
Subject(s) - axotomy , gap 43 protein , biology , cholinergic neuron , cholinergic , neuroscience , denervation , endocrinology , medicine , microbiology and biotechnology , central nervous system , immunohistochemistry , immunology
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.