PMID- 26298667
OWN - NLM
STAT- MEDLINE
DCOM- 20180116
LR  - 20181113
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 53
IP  - 7
DP  - 2016 Sep
TI  - Inhibitory Injury Signaling Represses Axon Regeneration After Dorsal Root Injury.
PG  - 4596-605
LID - 10.1007/s12035-015-9397-6 [doi]
AB  - Following injury to peripheral axons, besides increased cyclic adenosine 
      monophosphate (cAMP), the positive injury signals extracellular-signal-regulated 
      kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator 
      of transcription 3 (STAT-3) are locally activated and retrogradely transported to 
      the cell body, where they induce a pro-regenerative program. Here, to further 
      understand the importance of injury signaling for successful axon regeneration, 
      we used dorsal root ganglia (DRG) neurons that have a central branch without 
      regenerative capacity and a peripheral branch that regrows after lesion. Although 
      injury to the DRG central branch (dorsal root injury (DRI)) activated ERK, JNK, 
      and STAT-3 and increased cAMP levels, it did not elicit gain of intrinsic growth 
      capacity nor the ability to overcome myelin inhibition, as occurred after 
      peripheral branch injury (sciatic nerve injury (SNI)). Besides, gain of growth 
      capacity after SNI was independent of ERK and cAMP. Antibody microarrays of 
      dynein-immunoprecipitated axoplasm from rats with either DRI or SNI revealed a 
      broad differential activation and transport of signals after each injury type and 
      further supported that ERK, JNK, STAT-3, and cAMP signaling pathways are minor 
      contributors to the differential intrinsic axon growth capacity of both injury 
      models. Increased levels of inhibitory injury signals including GSK3beta and ROCKII 
      were identified after DRI, not only in axons but also in DRG cell bodies. In 
      summary, our work shows that activation and transport of positive injury signals 
      are not sufficient to promote increased axon growth capacity and that 
      differential modulation of inhibitory molecules may contribute to limited 
      regenerative response.
FAU - Mar, Fernando M
AU  - Mar FM
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, 4200, 
      Porto, Portugal.
AD  - Nerve Regeneration group, IBMC-Instituto de Biologia Molecular e Celular, 
      Universidade do Porto, 4150-180, Porto, Portugal.
FAU - Simoes, Anabel R
AU  - Simoes AR
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, 4200, 
      Porto, Portugal.
AD  - Nerve Regeneration group, IBMC-Instituto de Biologia Molecular e Celular, 
      Universidade do Porto, 4150-180, Porto, Portugal.
FAU - Rodrigo, Ines S
AU  - Rodrigo IS
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, 4200, 
      Porto, Portugal.
AD  - Nerve Regeneration group, IBMC-Instituto de Biologia Molecular e Celular, 
      Universidade do Porto, 4150-180, Porto, Portugal.
FAU - Sousa, Monica M
AU  - Sousa MM
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, 4200, 
      Porto, Portugal. msousa@ibmc.up.pt.
AD  - Nerve Regeneration group, IBMC-Instituto de Biologia Molecular e Celular, 
      Universidade do Porto, 4150-180, Porto, Portugal. msousa@ibmc.up.pt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150823
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Animals
MH  - Axons/*metabolism/pathology
MH  - Cells, Cultured
MH  - Female
MH  - Ganglia, Spinal/*injuries/*metabolism/pathology
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Male
MH  - Mice
MH  - Nerve Regeneration/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Sciatic Neuropathy/*metabolism/pathology
MH  - Signal Transduction/*physiology
MH  - rho-Associated Kinases/metabolism
OTO - NOTNLM
OT  - Axon regeneration
OT  - Dorsal root ganglia
OT  - GSK3beta
OT  - Injury signaling
OT  - ROCKII
EDAT- 2015/08/25 06:00
MHDA- 2018/01/18 06:00
CRDT- 2015/08/24 06:00
PHST- 2015/03/20 00:00 [received]
PHST- 2015/08/14 00:00 [accepted]
PHST- 2015/08/24 06:00 [entrez]
PHST- 2015/08/25 06:00 [pubmed]
PHST- 2018/01/18 06:00 [medline]
AID - 10.1007/s12035-015-9397-6 [pii]
AID - 10.1007/s12035-015-9397-6 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2016 Sep;53(7):4596-605. doi: 10.1007/s12035-015-9397-6. Epub 2015 
      Aug 23.