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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 orcid ; 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
; ; and
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
project
Nerve regeneration - signal transduktion mechanisms, timing and alternatives to nerve grafts
language
English
LU publication?
yes
id
70074cdd-3a50-4ee9-93a4-4b35315add12 (old id 131015)
date added to LUP
2016-04-01 11:41:32
date last changed
2022-05-18 19:30:53
@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}},
  doi          = {{10.1016/j.mcn.2004.07.001}},
  volume       = {{27}},
  year         = {{2004}},
}