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Inhibition of c-Jun phosphorylation reduces axonal outgrowth of adult rat nodose ganglia and dorsal root ganglia sensory neurons.

Lindwall, Charlotta LU ; Dahlin, Lars LU ; Lundborg, Göran LU and Kanje, Martin LU (2004) In Molecular and Cellular Neuroscience 27(3). p.267-279
Abstract
The role of c-Jun activation for survival and regeneration of sensory neurons is unclear. Here we report that c-Jun N-terminal kinase (JNK)-mediated c-Jun activation is important for axonal outgrowth of sensory neurons in rat nodose and dorsal root ganglia (DRG). Peripheral severance of the vagus or the sciatic nerve resulted in a massive and rapid, but transient increase of the activated JNK (p-JNK) in neuronal nuclei, followed by c-Jun phosphorylation and activating transcription factor-3 (ATF3) induction. JNK inhibition by the selective JNK inhibitors SP600125 and (D)-JNKI1 did not affect neuronal survival in explanted or dissociated ganglia, but dramatically reduced axonal outgrowth, c-Jun activation, and ATF3 induction. Using... (More)
The role of c-Jun activation for survival and regeneration of sensory neurons is unclear. Here we report that c-Jun N-terminal kinase (JNK)-mediated c-Jun activation is important for axonal outgrowth of sensory neurons in rat nodose and dorsal root ganglia (DRG). Peripheral severance of the vagus or the sciatic nerve resulted in a massive and rapid, but transient increase of the activated JNK (p-JNK) in neuronal nuclei, followed by c-Jun phosphorylation and activating transcription factor-3 (ATF3) induction. JNK inhibition by the selective JNK inhibitors SP600125 and (D)-JNKI1 did not affect neuronal survival in explanted or dissociated ganglia, but dramatically reduced axonal outgrowth, c-Jun activation, and ATF3 induction. Using retrograde labeling, we demonstrated that activated c-Jun (p-c-Jun) and ATF3 were associated with regenerative neurons. Taken together, our results suggest that JNK-mediated c-Jun activation is one of the first cell body reactions in response to nerve injury and that this activation and subsequent ATF3 induction are associated with axonal outgrowth. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular and Cellular Neuroscience
volume
27
issue
3
pages
267 - 279
publisher
Elsevier
external identifiers
  • wos:000224950000006
  • pmid:15519242
  • scopus:7244240786
ISSN
1044-7431
DOI
10.1016/j.mcn.2004.07.001
language
English
LU publication?
yes
id
70074cdd-3a50-4ee9-93a4-4b35315add12 (old id 131015)
date added to LUP
2007-07-23 12:29:06
date last changed
2017-09-17 04:36:20
@article{70074cdd-3a50-4ee9-93a4-4b35315add12,
  abstract     = {The role of c-Jun activation for survival and regeneration of sensory neurons is unclear. Here we report that c-Jun N-terminal kinase (JNK)-mediated c-Jun activation is important for axonal outgrowth of sensory neurons in rat nodose and dorsal root ganglia (DRG). Peripheral severance of the vagus or the sciatic nerve resulted in a massive and rapid, but transient increase of the activated JNK (p-JNK) in neuronal nuclei, followed by c-Jun phosphorylation and activating transcription factor-3 (ATF3) induction. JNK inhibition by the selective JNK inhibitors SP600125 and (D)-JNKI1 did not affect neuronal survival in explanted or dissociated ganglia, but dramatically reduced axonal outgrowth, c-Jun activation, and ATF3 induction. Using retrograde labeling, we demonstrated that activated c-Jun (p-c-Jun) and ATF3 were associated with regenerative neurons. Taken together, our results suggest that JNK-mediated c-Jun activation is one of the first cell body reactions in response to nerve injury and that this activation and subsequent ATF3 induction are associated with axonal outgrowth.},
  author       = {Lindwall, Charlotta and Dahlin, Lars and Lundborg, Göran and Kanje, Martin},
  issn         = {1044-7431},
  language     = {eng},
  number       = {3},
  pages        = {267--279},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Neuroscience},
  title        = {Inhibition of c-Jun phosphorylation reduces axonal outgrowth of adult rat nodose ganglia and dorsal root ganglia sensory neurons.},
  url          = {http://dx.doi.org/10.1016/j.mcn.2004.07.001},
  volume       = {27},
  year         = {2004},
}