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The Janus role of c-Jun: Cell death versus survival and regeneration of neonatal sympathetic and sensory neurons

Lindwall, Charlotta LU and Kanje, Martin LU (2005) In Experimental Neurology 196(1). p.184-194
Abstract
We investigated the functional outcome of c-Jun activation in sympathetic and sensory neurons of neonatal rat superior cervical ganglion (SCG) and dorsal root ganglion (DRG), respectively. Distinctly different roles of c-Jun activation have been suggested for these two types of neurons. In dissociated sympathetic neurons, c-Jun has been demonstrated to promote apoptosis, whereas in sensory neurons it stimulates axonal outgrowth. In organ-cultured ganglia, we found that c-Jun was activated within 24 h of explantation in both types of neurons, and that the JNK inhibitor SP600125 could mitigate this response. In both types of neurons, c-Jun activation was also reduced by NGF treatment. Inhibition of c-Jun activation did not affect the... (More)
We investigated the functional outcome of c-Jun activation in sympathetic and sensory neurons of neonatal rat superior cervical ganglion (SCG) and dorsal root ganglion (DRG), respectively. Distinctly different roles of c-Jun activation have been suggested for these two types of neurons. In dissociated sympathetic neurons, c-Jun has been demonstrated to promote apoptosis, whereas in sensory neurons it stimulates axonal outgrowth. In organ-cultured ganglia, we found that c-Jun was activated within 24 h of explantation in both types of neurons, and that the JNK inhibitor SP600125 could mitigate this response. In both types of neurons, c-Jun activation was also reduced by NGF treatment. Inhibition of c-Jun activation did not affect the viability of sympathetic neurons, whereas the number of apoptotic sensory neurons increased. Furthermore, inhibition of c-Jun reduced axonal outgrowth from both SCG and DRG. Thus, in organ culture, c-Jun activation may be required for axonal outgrowth and, at least in sensory neurons, it promotes survival. The role of ATF3, a neuronal marker of injury and a c-Jun dimerization partner, was also examined. We found an ATF3 induction in both SCG and DRG neurons, a response, which was reduced by JNK inhibition. The reduction of ATF3 upon JNK inhibition was much larger in DRG than in SCG, a result which might account for the higher number of apoptotic neurons in JNK inhibitor exposed DRG. Taken together, and contrary to our expectations, neonatal sympathetic and sensory neurons seem to respond to axonal injury similarly with respect to c-Jun activation, and in no case was this activation pro-apoptotic. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
development, SP600125 rat, NGF, SCG, c-Jun, DRG
in
Experimental Neurology
volume
196
issue
1
pages
184 - 194
publisher
Academic Press
external identifiers
  • pmid:16126201
  • wos:000232753000020
  • scopus:26244461183
ISSN
0014-4886
DOI
10.1016/j.expneurol.2005.07.022
language
English
LU publication?
yes
id
8174e645-151a-44c1-ae4b-d6c96dc67b8b (old id 218796)
date added to LUP
2007-09-28 15:46:55
date last changed
2017-05-21 03:28:30
@article{8174e645-151a-44c1-ae4b-d6c96dc67b8b,
  abstract     = {We investigated the functional outcome of c-Jun activation in sympathetic and sensory neurons of neonatal rat superior cervical ganglion (SCG) and dorsal root ganglion (DRG), respectively. Distinctly different roles of c-Jun activation have been suggested for these two types of neurons. In dissociated sympathetic neurons, c-Jun has been demonstrated to promote apoptosis, whereas in sensory neurons it stimulates axonal outgrowth. In organ-cultured ganglia, we found that c-Jun was activated within 24 h of explantation in both types of neurons, and that the JNK inhibitor SP600125 could mitigate this response. In both types of neurons, c-Jun activation was also reduced by NGF treatment. Inhibition of c-Jun activation did not affect the viability of sympathetic neurons, whereas the number of apoptotic sensory neurons increased. Furthermore, inhibition of c-Jun reduced axonal outgrowth from both SCG and DRG. Thus, in organ culture, c-Jun activation may be required for axonal outgrowth and, at least in sensory neurons, it promotes survival. The role of ATF3, a neuronal marker of injury and a c-Jun dimerization partner, was also examined. We found an ATF3 induction in both SCG and DRG neurons, a response, which was reduced by JNK inhibition. The reduction of ATF3 upon JNK inhibition was much larger in DRG than in SCG, a result which might account for the higher number of apoptotic neurons in JNK inhibitor exposed DRG. Taken together, and contrary to our expectations, neonatal sympathetic and sensory neurons seem to respond to axonal injury similarly with respect to c-Jun activation, and in no case was this activation pro-apoptotic.},
  author       = {Lindwall, Charlotta and Kanje, Martin},
  issn         = {0014-4886},
  keyword      = {development,SP600125 rat,NGF,SCG,c-Jun,DRG},
  language     = {eng},
  number       = {1},
  pages        = {184--194},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {The Janus role of c-Jun: Cell death versus survival and regeneration of neonatal sympathetic and sensory neurons},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2005.07.022},
  volume       = {196},
  year         = {2005},
}