K.B. and L.K. contributed equally to this work.
Selective up-regulation of the growth arrest DNA damage-inducible gene Gadd45 alpha in sensory and motor neurons after peripheral nerve injury
Article first published online: 11 AUG 2003
European Journal of Neuroscience
Volume 18, Issue 4, pages 911–922, August 2003
How to Cite
Befort, K., Karchewski, L., Lanoue, C. and Woolf, C. J. (2003), Selective up-regulation of the growth arrest DNA damage-inducible gene Gadd45 alpha in sensory and motor neurons after peripheral nerve injury. European Journal of Neuroscience, 18: 911–922. doi: 10.1046/j.1460-9568.2003.02827.x
Present address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, UMR7104, Parc d'Innovation, 1 rue Laurent Fries BP 10142, 67404 Illkirch Cedex, C.U. Strasbourg, France.
- Issue published online: 12 AUG 2003
- Article first published online: 11 AUG 2003
- Received 11 April 2003, revised 10 June 2003, accepted 13 June 2003
- activating transcription factor 3;
- dorsal root ganglion;
- spinal cord
The growth arrest and DNA damage-inducible gene 45 alpha (Gadd45a) was one of 240 genes found previously by high density oligonucleotide microarray analysis to be regulated in the rat L4 and L5 dorsal root ganglia 3 days after transection of the sciatic nerve (>four-fold up-regulation). The Gadd45a mRNA expression profile investigated by northern blot, RNase protection assay and in situ hybridization in the rat shows negligible constitutive mRNA levels in embryonic, neonatal or adult intact dorsal root ganglia. Within 24 h of a sciatic nerve injury, a very large induction is found that persists for as long as regeneration of injured fibres is prevented by peripheral nerve ligation. When axons are allowed to regrow following sciatic nerve crush injury, Gadd45a expression is terminated at later time points, when levels of other markers of injury return towards normal. Colocalization with activating transcription factor 3-LI and c-jun mRNA implies that all peripherally injured primary sensory and motor neurons express Gadd45a mRNA. Injury to the central axons of dorsal root ganglion neurons produces only a minimal induction of Gadd45a while peripheral inflammation is without effect. Gadd45a is a specific marker of the presence of peripheral axonal injury in adult primary sensory and motor neurons.