Original Research ARTICLE

Front. Neurol., 17 May 2011 | http://dx.doi.org/10.3389/fneur.2011.00030

Activating transcription factor 3, a useful marker for regenerative response after nerve root injury

  • 1 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • 2 Neurology Unit, Division of Internal Medicine, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
  • 3 Department of Neuroscience, Section of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden

Activating transcription factor 3 (ATF3) is induced in various tissues in response to stress. In this experiment, ATF3 expression was studied in adult rats subjected either to a dorsal or ventral root avulsion (VRA; L4-6), or sciatic nerve transection (SNT). Post-operative survival times varied between 1.5 h and 3 weeks. In additional experiments an avulsed ventral root was directly replanted to the spinal cord. Dorsal root ganglias (DRGs) from humans exposed to traumatic dorsal root avulsions were also examined. After SNT ATF3 immunoreactivity (ATF3 IR) was detected in a few DRG neurons already 6 h after the lesion. After 24 h the number had clearly increased and still at 3 weeks DRG neurons remained labeled. In the ventral horn, ATF3 IR in motoneurons (MN) was first detected 24 h after the SNT, and still 3 weeks post-operatively lesioned MN showed ATF3 labeling. After a VRA many spinal MN showed ATF3 IR already after 3 h, and after 6 h all MN were labeled. At 3 weeks a majority of the lesioned MN had died, but all the remaining ones were labeled. When an avulsed ventral root was directly replanted, MN survived and were still labeled at 5 weeks. In DRG, a few neurons were labeled already at 1.5 h after a dorsal root avulsion. At 24 h the number had increased but still only a minority of the neurons were labeled. At 3 days the number of labeled neurons was reduced, and a further reduction was at hand at 7 days and 3 weeks. In parallel, in humans, 3 days after a traumatic dorsal root avulsion, only a few DRG neurons showed ATF3 IR. At 6 weeks no labeled neurons could be detected. These facts imply that ATF3 response to axotomy involves a distance-dependent mechanism. ATF3 also appears to be a useful and reliable neuronal marker of nerve lesions even in humans. In addition, ATF3 up-regulation in both motor and sensory neurons seems to be linked to regenerative competence.

Keywords: ATF3, nerve lesion, motoneuron, dorsal root ganglia, regeneration, spinal cord

Citation: Lindå H, Sköld MK and Ochsmann T (2011) Activating transcription factor 3, a useful marker for regenerative response after nerve root injury. Front. Neur. 2:30. doi: 10.3389/fneur.2011.00030

Received: 06 February 2011; Paper pending published: 16 March 2011;
Accepted: 04 May 2011; Published online: 17 May 2011.

Edited by:

Thomas Carlstedt, University College London, UK

Reviewed by:

Steve N.S. Cheung, University of Tasmania, Australia
Peter Shortland, Barts and The London School of Medicine and Dentistry, UK

Copyright: © 2011 Lindå, Sköld and Ochsmann. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Hans Lindå, Neurology Unit, Division of Internal Medicine, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden. e-mail: hans.linda@ki.se