Regenerative and survival capabilities of Purkinje cells overexpressing c-Jun.
Following axotomy, cerebellar Purkinje cells (PCs) do not elongate their axons, even in a favourable environment, and are resistant to death. They have no constitutive presence of common growth-associated proteins, such as GAP-43 and c-Jun. Previous experiments show that injured transgenic PCs overexpressing GAP-43 exhibit a profuse sprouting along the axon and at its severed end. Nevertheless, the lesioned axons are unable to regenerate either spontaneously or into growth-permissive environments. In addition, a considerable number of GAP-43 transgenic PCs degenerate after injury. c-Jun is an inducible transcription factor expressed in axotomized central neurons and regenerating peripheral neurons. It also contributes to programmed cell death during development. To test whether c-Jun could modify the response of PCs to axotomy or enhance the growth/death phenomena of GAP-43 Purkinje neurons, we generated transgenic mice overexpressing c-Jun in PCs. However, c-Jun upregulation did not affect the adult intact phenotype of these neurons and their regenerative and survival capabilities after axotomy. Also in the cross-bred GAP-43/c-Jun mice, c-Jun did not modify the response of GAP-43 PCs to axotomy. By contrast, in organotypic cultures of cerebellum taken from 9-day-old-pups, the survival capabilities of PCs overexpressing c-Jun decreased, in association with a consistent c-Jun phosphorylation. On the whole our data show that c-Jun alone is unable to trigger regenerative or degenerative phenomena in PCs and suggest that the cellular action of this early gene in developing and mature neurons strongly depends on interplaying intracellular signals.
Carulli
Daniela
D
Rita Levi-Montalcini Centre for Brain Repair, Department of Neuroscience, University of Turin, C. Raffaello 30, 10125 Turin, Italy. daniela.carulli@unito.it
Buffo
Annalisa
A
Botta
Cristina
C
Altruda
Fiorella
F
Strata
Piergiorgio
P
D000818:Animals; D019771:Axotomy; D015153:Blotting, Western; D016923:Cell Death / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D019922:GAP-43 Protein / Q000235:genetics*; D016758:Genes, jun; D006652:Histological Techniques; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D015854:Up-Regulation
D019922:GAP-43 Protein